tag:theconversation.com,2011:/us/topics/mrna-vaccines-104443/articlesmRNA vaccines – The Conversation2024-01-04T13:45:37Ztag:theconversation.com,2011:article/2151992024-01-04T13:45:37Z2024-01-04T13:45:37ZDrugs of the future will be easier and faster to make, thanks to mRNA – after researchers work out a few remaining kinks<figure><img src="https://images.theconversation.com/files/567750/original/file-20240103-21-2oxdyb.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2448%2C1224&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Two hurdles mRNA drugs face are a short half-life and impurities that trigger immune responses.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/on-white-background-royalty-free-image/1411871727">BlackJack3D/iStock via Getty Images Plus</a></span></figcaption></figure><p>Vaccines have been reliably and affordably protecting people from diseases worldwide <a href="https://theconversation.com/from-smallpox-to-polio-vaccine-rollouts-have-always-had-doubters-but-they-work-in-the-end-161803">for centuries</a>. Until the COVID-19 pandemic, however, vaccine development was still a long and idiosyncratic process. Traditionally, researchers had to tailor manufacturing processes and facilities for each vaccine candidate, and the scientific knowledge gained from one vaccine was often not directly transferable to another. </p>
<p>But the COVID-19 mRNA vaccines brought a new approach to vaccine development that has far-reaching implications for how researchers make drugs to treat many other diseases. </p>
<p><a href="https://scholar.google.com/citations?user=C49y7YQAAAAJ&hl=en">I am a biochemist</a>, and <a href="https://www.umassmed.edu/LiLab/">my lab</a> at UMass Chan Medical School focuses on developing better ways to use mRNA as a drug. Although there are <a href="https://theconversation.com/customizing-mrna-is-easy-and-thats-what-makes-it-the-next-frontier-for-personalized-medicine-a-molecular-biologist-explains-216127">many possibilities</a> for what researchers can use mRNA to treat, some important limitations remain. Better understanding how mRNA-based drugs interact with the immune system and how they are degraded in human cells can help lead to safe, durable and effective treatments for a wide range of diseases.</p>
<h2>Some basics of mRNA drugs</h2>
<p>Messenger RNA, or mRNA, is made of four building blocks denoted by the letters A, C, G and U. The sequence of letters in an mRNA molecule conveys genetic information that directs how a protein is made. </p>
<p>An mRNA drug comprises two essential components: mRNA molecules, which code for desired proteins, and the lipid molecules – such as phospholipids and cholesterol – that encapsulate them. These <a href="https://doi.org/10.1016/j.jconrel.2015.08.007">mRNA-lipid nanoparticles, or LNPs</a>, are tiny spheres <a href="https://doi.org/10.1016/j.ymthe.2017.03.013">about 100 nanometers in diameter</a> that protect mRNA from degradation and facilitate its delivery into target cells. </p>
<p>Once inside cells, mRNA molecules instruct the cell’s machinery to produce the target protein required for a desired therapeutic effect. For example, the mRNA in the Pfizer-BioNTech and Moderna <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">COVID-19 vaccines</a> directs cells to produce a harmless version of the virus’ spike protein that trains the immune system to recognize and better prepare for potential infection. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/v-NEr3KCug8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The science behind COVID-19 mRNA vaccines has been decades in the making.</span></figcaption>
</figure>
<p>From a drug development perspective, mRNA drugs offer significant advantages over traditional drugs because they are <a href="https://theconversation.com/customizing-mrna-is-easy-and-thats-what-makes-it-the-next-frontier-for-personalized-medicine-a-molecular-biologist-explains-216127">easily programmable</a>. Hundreds of pounds of mRNA can be made from readily available DNA templates, such that producing a different mRNA drug is as simple as changing the corresponding DNA templates. </p>
<p>More importantly, different mRNA drugs produced by the same set of methods will have similar properties. They will be delivered to the same tissues, trigger similar levels of immune responses and degrade in similar ways. This predictability significantly reduces the development risks and financial costs of developing mRNA drugs.</p>
<p>In addition to being easy to program, mRNA drugs have several other unique properties. For example, just like the mRNAs your body naturally produces, therapeutic mRNAs have a short half-life in cells: <a href="https://doi.org/10.1016%2Fj.jconrel.2015.08.007">about one day</a>. As a result, current mRNA technology is ideal for treatments that aren’t meant to last long in the body. </p>
<p>This is why vaccines are popular candidates for mRNA technology: They provide long-term protection against disease after brief exposure to the drug with few side effects. There are currently <a href="https://www.mdpi.com/1422-0067/24/3/2700">more than 30 mRNA vaccine candidates</a>, not including vaccines for COVID-19, in clinical trials.</p>
<h2>Self vs. nonself</h2>
<p>Another critical feature of mRNA drugs is their intrinsic ability to stimulate the immune system. This may sound paradoxical – after all, your cells already contain large amounts of mRNAs. Why would other mRNAs activate your immune system? How does your immune system distinguish between self and nonself mRNAs?</p>
<p>The first reason involves location. Therapeutic mRNAs enter cells using endosomes – sacs made of the cell’s membrane that take in materials from the cell’s environment. Your immune system can detect mRNA in endosomes because this is usually a sign of an RNA virus infection – cellular mRNAs normally don’t enter endosomes. When your immune system labels therapeutic mRNAs as viral material, it triggers <a href="https://doi.org/10.1016/j.immuni.2005.06.008">a strong inflammatory response</a> that can lead to severe side effects. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/567748/original/file-20240103-25-lqiluh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram showing molecules entering a depression in the cell membrane which closes off to form a sac" src="https://images.theconversation.com/files/567748/original/file-20240103-25-lqiluh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567748/original/file-20240103-25-lqiluh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567748/original/file-20240103-25-lqiluh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567748/original/file-20240103-25-lqiluh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567748/original/file-20240103-25-lqiluh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567748/original/file-20240103-25-lqiluh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567748/original/file-20240103-25-lqiluh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Endocytosis is the process by which material outside the cell, such as mRNA molecules, is engulfed within the cell.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/endocytosis-process-cells-absorb-external-royalty-free-illustration/1621615509">alfa md/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>One solution to this problem is to modify mRNA’s building blocks – specifically, changing the U, or uridine, to its chemical cousins, <a href="https://doi.org/10.1016/j.immuni.2005.06.008">pseudouridine</a> and <a href="https://doi.org/10.1016/j.jconrel.2015.08.051">N1-methylpseudouridine</a>. This subtle chemical change prevents the unwanted immune response while allowing the therapeutic mRNA to <a href="https://doi.org/10.1038%2Fmt.2008.200">direct the cell to make the protein it encodes</a>. The <a href="https://theconversation.com/tenacious-curiosity-in-the-lab-can-lead-to-a-nobel-prize-mrna-research-exemplifies-the-unpredictable-value-of-basic-scientific-research-214770">2023 Nobel Prize in physiology or medicine</a> was awarded to the scientists who made this breakthrough discovery. Both the Pfizer-BioNTech and Moderna <a href="https://doi.org/10.1021/acscentsci.1c00197">COVID-19 mRNA vaccines</a> use this technique.</p>
<p>The second source of unwanted immune response is impurities from mRNA production. To prepare mRNA from a DNA template, scientists use a protein called <a href="https://www.nature.com/scitable/definition/rna-polymerase-106/">RNA polymerase</a> that tends to make a small amount of side product called <a href="https://doi.org/10.1093/nar/gkr695">double-stranded RNA</a>. Unlike mRNA, which is single-stranded, double-stranded RNA has two chains that form a double helix. RNA viruses also form double-stranded RNA when they replicate, and exposing cells to double-stranded RNA can lead to a strong immune response.</p>
<p>Removing double-stranded RNA is challenging, especially at the industrial scale. Fortuitously, for mRNA vaccines, the residual amount of double-stranded RNA can stimulate the immune system to <a href="https://doi.org/10.1038/s41590-022-01163-9">enhance antibody responses</a>. However, for applications other than vaccines, a cleaner RNA product is necessary to reduce side effects.</p>
<h2>Moving beyond vaccines</h2>
<p>Although mRNA has the potential to transform drug development for various medical purposes, careful consideration is required to identify targets that align with the technology’s strengths.</p>
<p>For example, because there is currently a limit to how long mRNA can last in the body, treatments that need a protein to be present for only a short period of time to achieve a lasting therapeutic effect are ideal. One promising example in development is using mRNA that encodes CRISPR-Cas9 gene-editing proteins to knock out genes that cause specific diseases.</p>
<p>Researchers are exploring this strategy to develop a single-dose treatment for <a href="https://doi.org/10.1056/NEJMoa2107454">hereditary transthyretin amyloidosis</a>, a rare genetic disease caused by the accumulation of misfolded proteins in the heart and nerves. This disease is an ideal target for mRNA-based CRISPR gene therapy because the target protein is produced by the liver. Because most drugs pass through the liver, this makes it easier to deliver CRISPR-Cas9 mRNA to its target. In the next few years, a new generation of more precise <a href="https://doi.org/10.1038/d41586-023-03797-7">mRNA-based genome editing therapies</a> will enter clinical trials.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/567751/original/file-20240103-17-vch2ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of SARS-CoV-2 virus particles lining the a few vesicles in a cell" src="https://images.theconversation.com/files/567751/original/file-20240103-17-vch2ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/567751/original/file-20240103-17-vch2ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/567751/original/file-20240103-17-vch2ou.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/567751/original/file-20240103-17-vch2ou.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/567751/original/file-20240103-17-vch2ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=564&fit=crop&dpr=1 754w, https://images.theconversation.com/files/567751/original/file-20240103-17-vch2ou.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=564&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/567751/original/file-20240103-17-vch2ou.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=564&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Because the virus that causes COVID-19 (gold) and other RNA viruses enter cells through endosomes, mRNA drug impurities can elicit similar immune responses.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/2mrqrnx">NIAID/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>For treatments that need a specific protein to be present in the body for long periods of time or need to prompt little to no immune reaction, further advancements in mRNA technology are necessary to extend mRNA’s half-life and eliminate immune-triggering contaminants. Notable new developments in these areas include using <a href="https://doi.org/10.1101/2021.03.29.437587">computational algorithms</a> to optimize mRNA sequences in ways that enhance their stability and <a href="https://doi.org/10.1038/s41587-022-01525-6">engineering RNA polymerases</a> that introduce fewer side products that may cause an immune response. </p>
<p>Further advancements have the potential to enable a new generation of safe, durable and effective mRNA therapeutics for applications beyond vaccines.</p><img src="https://counter.theconversation.com/content/215199/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Li Li receives funding from NIH. </span></em></p>The COVID-19 pandemic demonstrated the promise of using mRNA as medicine. But before mRNA drugs can go beyond vaccines, researchers need to identify the right diseases to treat.Li Li, Assistant Professor of Biomedical Sciences, UMass Chan Medical SchoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2195412023-12-18T14:48:37Z2023-12-18T14:48:37ZmRNA COVID vaccines make ‘unintended proteins’ – we’ve discovered how to fix this problem<p>MRNA, a type of genetic material that provides the instructions your cells need in order to make proteins, used to be a term mainly used by scientists. But since COVID arrived many of us are now familiar with it thanks to the mRNA-based vaccines.</p>
<p>The people behind the discoveries that made mRNA-based vaccines and treatments a possibility were awarded the <a href="https://theconversation.com/nobel-prize-in-medicine-awarded-to-mrna-pioneers-heres-how-their-discovery-was-integral-to-covid-vaccine-development-214763">Nobel prize</a> earlier this year. That work showed that some of the mRNA’s chemical letters that make up its alphabet need to be switched out for synthetic equivalents for this technology to be viable. </p>
<p>However, these artificial versions are causing <a href="https://www.science.org/content/article/mrna-vaccines-may-make-unintended-proteins-there-s-no-evidence-harm">“unintended proteins”</a> to be made and hence immune responses to these proteins. The question is now: can we prevent this? The answer is yes we can. And it’s a straightforward fix.</p>
<p>Vaccines using all-natural mRNA don’t work. Our immune system recognises them as foreign to the body and mounts a response to remove them, just like it would to any invading germ. </p>
<p>The Nobel prize-winning work of Katalin Karikó and Drew Weissman essentially gave the injected mRNA an invisibility cloak – the synthetic “letters” – preventing its detection and destruction by our immune system. This allows safe delivery of the mRNA to cells to do its job. </p>
<p>In the case of the COVID vaccines, our cells make the spike protein and our immune system makes antibodies against it, protecting us from severe disease.</p>
<p>Micro-protein factories called ribosomes read the mRNA instructions to make proteins. They read the code three chemical letters at a time. Each triplet codes for an amino acid – a single building block of a protein. </p>
<p>The ribosome moves along to the next three letters and identifies which amino acid is next to be added to the growing protein. This repeats until it reaches the end of the mRNA instructions.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/A7gSWqpXRsc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">How mRNA works.</span></figcaption>
</figure>
<p>So where do the “unintended proteins” come from? They are created in the same way, but errors can occur if the ribosome reaches a string of these synthetic chemical letters in the mRNA. </p>
<p>The ribosome can slip, essentially losing its place in what it is reading. For instance, rather than reading THE CAT ATE THE FAT RAT, it reads the message as THE CAT A TET HEF ATR AT, resulting in the production of a different protein.</p>
<p>In a <a href="https://www.nature.com/articles/s41586-023-06800-3">recent study</a>, published in Nature, my colleagues and I revealed that these unintended proteins were produced in a third of the 21 people who participated in the study and were vaccinated with the Pfizer mRNA vaccine. Also, those people generated an immune response against these proteins.</p>
<p>Beyond the strength of the data from the original clinical trial, the safety of the Pfizer vaccine has been re-established by observing millions of vaccine recipients, and the benefits still outweigh the risks for those still recommended to receive it. So our latest study should not affect the safety assessment of existing mRNA COVID vaccines. </p>
<h2>No evidence of harm</h2>
<p>The data is clear: there is no evidence linking unintended proteins and immune responses with harm. </p>
<p>It’s important to note that humans regularly encounter unintended proteins and generate harmless immune responses, as seen with proteins produced from our food or by harmless gut bacteria. These immune responses, which occur in all of us constantly, are controlled by our immune system to prevent them from causing damage to our bodies.</p>
<p>These unintended proteins arising from mRNA vaccines are not random. We know where errors can occur in the mRNA code and can fix them to prevent issues in future mRNA-based therapies.</p>
<p>Luckily, nature provides a fail-safe we can take advantage of. With only 20 different amino acids, but 64 possible sets of three chemical letters, more than one triplet codes for a given amino acid. When designing new mRNA therapeutics, triplets prone to errors can be identified using a simple algorithm and replaced with an alternative spelling of the same code – similar to “mum” and “mom”.</p>
<p>MRNA therapies will be gamechanging for medicine. They are easy to make, can be produced rapidly and are easily modified. Most excitingly, this technology could be used to treat a wide range of diseases, including cancer. </p>
<p>Cancer treatment has been revolutionised by immunotherapy – which uses the patient’s immune system to fight the cancer, but its effectiveness varies. The main hope for making immunotherapy more successful lies in designing mRNA-based cancer vaccines that are personalised to the patient.</p>
<p>This finding raises the new possibility that unintended proteins could be generated by any mRNA therapeutic. Also, it is not possible to be sure that, in the context of cancer treatment, unintended proteins and the immune responses they trigger will be harmless. However, this discovery gives new insights into how these unintended proteins are generated and, most importantly, how modifications can be made to prevent these from arising.</p><img src="https://counter.theconversation.com/content/219541/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anne Willis receives funding from Medical Research Council UK and Wellcome Trust LEAP</span></em></p><p class="fine-print"><em><span>James Thaventhiran does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>mRNA vaccines are very safe, but this problem needed to be fixed for future mRNA therapies.James Thaventhiran, MRC Investigator, University of CambridgeAnne Willis, Professor of Toxicology Department of Pharmacology, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2161272023-12-12T13:22:36Z2023-12-12T13:22:36ZCustomizing mRNA is easy, and that’s what makes it the next frontier for personalized medicine − a molecular biologist explains<figure><img src="https://images.theconversation.com/files/564366/original/file-20231207-25-2zr2cm.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1499&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">One of the advantages of mRNA is its scalability.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/genetic-engineering-dna-royalty-free-illustration/1310083278">DrAfter123/DigitalVision Vectors via Getty Images</a></span></figcaption></figure><p>While using mRNA as medicine is new, mRNA has been inside you for your entire life. The cells in your body create mRNAs that serve as instructions to make specific proteins you need to function. Researchers can create new mRNAs to correct those instructions when they aren’t working.</p>
<p>I am a <a href="https://scholar.google.com/citations?user=HQmZPBYAAAAJ&hl=en">molecular biologist</a> who studies how cells control their mRNAs to make the proteins they need, a basic question of how life works at the cellular level. While most scientists studying mRNAs are not creating new drugs, this fundamental understanding of how mRNA works <a href="https://theconversation.com/tenacious-curiosity-in-the-lab-can-lead-to-a-nobel-prize-mrna-research-exemplifies-the-unpredictable-value-of-basic-scientific-research-214770">laid the foundation</a> for other scientists to create effective mRNA medicines like <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">COVID-19 vaccines</a>. </p>
<p>By tweaking these instructions, scientists can create powerful new medicines to repair a variety of problems in your cells.</p>
<h2>What does mRNA do?</h2>
<p>To understand what the mRNAs in your cells are doing for you, let’s start with its more well-known relative, DNA. </p>
<p>DNA is like a set of cookbooks full of different recipes, or genes, to make proteins. People make <a href="https://www.broadinstitute.org/blog/putting-proteins-their-place">about 100,000 different proteins</a> that are essential for <a href="https://theconversation.com/what-is-a-protein-a-biologist-explains-152870">normal function</a>, such as breaking down nutrients and carrying out other important chemical reactions.</p>
<p>When cells need to make one of those proteins, they don’t read the recipe directly from DNA. Instead, they make a copy in the form of a similar molecule – that’s <a href="https://www.genome.gov/genetics-glossary/messenger-rna">the mRNA</a>. The “m” stands for messenger, as mRNA contains the message, or recipe, that codes for a protein. About <a href="https://doi.org/10.1016/j.cell.2014.02.033">one-third of a cell’s energy</a> is devoted to maintaining the proteins you need, so cells are well equipped to recognize, use and then destroy mRNA once it’s no longer needed.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/564367/original/file-20231207-19-o117b3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram illustrating flow of DNA transcription to RNA translation to protein" src="https://images.theconversation.com/files/564367/original/file-20231207-19-o117b3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/564367/original/file-20231207-19-o117b3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564367/original/file-20231207-19-o117b3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564367/original/file-20231207-19-o117b3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564367/original/file-20231207-19-o117b3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564367/original/file-20231207-19-o117b3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564367/original/file-20231207-19-o117b3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">mRNA is the intermediary between DNA and protein.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/transcription-and-translation-dna-mrna-and-royalty-free-illustration/1474947465">Rujirat Boonyong/iStock via Getty Images</a></span>
</figcaption>
</figure>
<p>The language of mRNA is made of four <a href="https://www.genome.gov/genetics-glossary/Nucleotide">building blocks called nucleotides</a>, nicknamed A, U, C and G. The recipe to make a protein contains only three-letter words, meaning there are just 64 possible words. Scientists know exactly which words correspond to each protein building block, so they can easily read an mRNA recipe and know what protein will be made. Mutations in the DNA cookbook can alter or delete an mRNA recipe, leading to disease-causing mistakes in critical proteins.</p>
<h2>Why do mRNAs make great medicine?</h2>
<p>While mRNA has been within us all along, it took <a href="https://doi.org/10.1038/d41586-021-02483-w">decades of research</a> for scientists to understand how cells recognize mRNA and use it to make protein. But it eventually became clear that mRNA could be a powerful medical tool.</p>
<p>Since scientists understand how mRNAs code for proteins, they can easily create recipes for any protein. These recipes can be <a href="https://doi.org/10.1038/s41587-022-01430-y">edited to meet the needs</a> of the patient, whether this means providing a whole new mRNA recipe or tweaking an existing one to make a slight variation of the protein.</p>
<p>Producing mRNA treatments <a href="https://doi.org/10.1038/nrd.2017.243">is also scalable</a> because scientists can make large amounts of mRNA in the lab. The method to make one mRNA is the same for all mRNAs, unlike typical drugs where each compound has its own unique chemistry and requires different manufacturing methods. It’s like learning how to make risotto: Once you’ve learned the basic recipe, you can make endless variations.</p>
<p>Another benefit of using mRNAs as drugs are cells’ <a href="https://doi.org/10.1038/s41580-022-00512-8">natural ability to destroy them</a> when they aren’t needed. Since mRNAs aren’t permanent, doses can be easily changed to meet the changing needs of the patient.</p>
<h2>mRNA vaccines beyond COVID-19</h2>
<p>The <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">COVID-19 vaccines</a> from Moderna and Pfizer-BioNTech are the first mRNA-based medicines to gain FDA approval. When these vaccines are injected into your arm, the mRNA is absorbed into some of your cells, which read the mRNA recipe and make the spike protein the virus uses to invade cells. Your immune system recognizes this spike protein as foreign and makes antibodies that prepare your body to attack the virus if you encounter it later.</p>
<p>These mRNA vaccines demonstrate the <a href="https://theconversation.com/how-can-scientists-update-coronavirus-vaccines-for-omicron-a-microbiologist-answers-5-questions-about-how-moderna-and-pfizer-could-rapidly-adjust-mrna-vaccines-172943">flexibility of mRNA-based therapies</a>. As the virus that causes COVID-19 mutates, new viral variants can evade existing antibodies and cause new waves of illness. However, scientists are able to sequence new mRNA recipes based on these variants and tweak the vaccine recipes to match them. Boosters containing these edited recipes teach your body to make new antibodies that target the latest versions of the viral spike protein.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/7DlcRSvuvnw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The Pfizer-BioNTech and Moderna COVID-19 vaccines were the first to use mRNA for immunization.</span></figcaption>
</figure>
<p>There are already clinical trials underway for other mRNA-based vaccines, including vaccines for <a href="https://theconversation.com/how-do-you-make-a-universal-flu-vaccine-a-microbiologist-explains-the-challenges-and-how-mrna-could-offer-a-promising-solution-195807">seasonal flu</a>, <a href="https://theconversation.com/how-mrna-and-dna-vaccines-could-soon-treat-cancers-hiv-autoimmune-disorders-and-genetic-diseases-170772">herpes</a> and <a href="https://theconversation.com/fdas-approval-of-the-worlds-first-vaccine-against-rsv-will-offer-a-new-tool-in-an-old-fight-4-questions-answered-205111">respiratory syncytial virus</a>. </p>
<p>There are also many more vaccines in earlier stages of development to combat diseases like <a href="https://www.forbes.com/sites/roberthart/2023/04/11/vaccines-for-lyme-disease-and-norovirus-moderna-working-on-shots-targeting-tick-borne-infection-and-vomiting-bug/">norovirus, Lyme disease</a>, <a href="https://doi.org/10.1016/S1473-3099(22)00764-2">Zika</a> and <a href="https://www.pfizerclinicaltrials.com/our-research/vaccines">shingles</a>. </p>
<h2>mRNA as treatment for disease</h2>
<p>The potential for mRNA-based medicine extends beyond vaccines to prevent infectious disease. One example is the <a href="https://theconversation.com/modernas-experimental-cancer-vaccine-treats-but-doesnt-prevent-melanoma-a-biochemist-explains-how-it-works-197003">use of mRNA to treat cancer</a>. </p>
<p>Some mRNA cancer treatments work like vaccines by training your immune system to specifically target cancer cells. As cancer cells grow, they rapidly gain mutations in many genes. Cancer vaccines contain mRNA recipes based on mutations commonly found in certain types of tumors. When injected into the body, the mRNAs from the vaccines allow normal cells to make those mutated proteins and broadcast them to the immune system, ramping up production of antibodies. These antibodies bind to cancer cells and mark them for immune attack.</p>
<p>Finding the <a href="https://theconversation.com/every-cancer-is-unique-why-different-cancers-require-different-treatments-and-how-evolution-drives-drug-resistance-199249">correct protein target for a given cancer</a> is essential. Ideally, the target is unique to the cancer cell so the immune system doesn’t attack healthy cells. The target protein should also be easy for the immune system to sense, making surface proteins good targets. Cancer vaccines, like <a href="https://doi.org/10.1038/s41586-020-2537-9">BioNTech’s BNT-111</a> for melanoma, target the most common cancer mutations in hope of helping many patients. But patients won’t benefit from the treatment if their cancer cells don’t have those particular mutations.</p>
<p>Because it is so easy to change the mRNA recipes, cancer vaccines can be part of a <a href="https://www.genome.gov/genetics-glossary/Personalized-Medicine">personalized medicine plan</a> where doctors sample a patient’s tumor, sequence key genes and adjust the mRNA treatment to include recipes specific to that patient’s cancer. Clinical trials using this <a href="https://www.mskcc.org/news/can-mrna-vaccines-fight-pancreatic-cancer-msk-clinical-researchers-are-trying-find-out">personalized approach for pancreatic cancer</a> are underway. </p>
<h2>The future of mRNA-based medicine</h2>
<p>Many diseases arise from cells making the wrong protein, a mutant version of protein or too little of the normal protein. If scientists can deliver a corrected version of the mRNA recipe to enough affected cells, then the mRNA will provide the means to make the proper protein.</p>
<p>Scientists are exploring the use of mRNA to treat <a href="https://spectrum.ieee.org/mrna-therapy-damaged-heart">heart disease</a>, <a href="https://theconversation.com/vaccination-to-prevent-dementia-new-research-suggests-one-way-viral-infections-can-accelerate-neurodegeneration-197009">neurodegenerative disease</a>, <a href="https://doi.org/10.1186/s41232-023-00285-3">bone loss</a> and much more. Although most of these studies are still very early in development, they provide hope for future treatments using mRNA for protein replacement therapies. </p>
<p>For example, one mRNA drug increases the <a href="https://www.nature.com/articles/s41467-019-08852-4">formation of new blood vessels</a>, which can improve <a href="https://www.healthline.com/health/diabetes/diabetes-and-wound-healing#what-leads-to-slow-healing">wound healing in diabetic patients</a> who have poor blood circulation and higher amputation risks. Another example is using mRNAs to treat <a href="https://clinicaltrials.gov/study/NCT04159103">propionic acidemia</a>, a disease where children have low levels of two liver proteins that normally prevent toxic byproducts from building up in the body.</p>
<p>The ability to easily customize and produce mRNA increases their potential as effective, personalized therapies – with fewer side effects – that can help many people.</p><img src="https://counter.theconversation.com/content/216127/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Angie Hilliker has received funding from the National Institutes of Health. </span></em></p>From COVID-19 vaccines to cancer treatments and beyond, the flexibility of mRNA-based therapies gives them the potential to prevent and treat many types of diseases.Angie Hilliker, Associate Professor of Biology, University of RichmondLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2157042023-10-26T03:37:37Z2023-10-26T03:37:37ZCOVID proved the therapeutic potential of RNA technology – making it more available is the next goal<figure><img src="https://images.theconversation.com/files/555932/original/file-20231025-30-xeztbl.jpg?ixlib=rb-1.1.0&rect=53%2C71%2C5937%2C3269&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/rna-epigenetics-concept-3d-illustration-2040062156">Shutterstock/ART-ur</a></span></figcaption></figure><p>The recent award of the 2023 Nobel prize in physiology or medicine to <a href="https://theconversation.com/nobel-prize-in-medicine-awarded-to-mrna-pioneers-heres-how-their-discovery-was-integral-to-covid-vaccine-development-214763">Katalin Karikó and Drew Weissman</a> highlights the growing importance of RNA technology in the medical world, with many potential applications beyond COVID vaccines. </p>
<p>But until now, one of the major hindrances in making this technology more widely available globally, and in translating research into clinical use, has been the need for proprietary products, often licensed by pharmaceutical companies. </p>
<p>Detailed methodology to deliver RNA vaccines to cells was also not easily available to the research community. </p>
<p>For these reasons we have <a href="https://currentprotocols.onlinelibrary.wiley.com/doi/full/10.1002/cpz1.898">published a protocol</a> detailing how to make and package RNA with commercially available reagents.</p>
<h2>How RNA therapies work</h2>
<p>RNA stands for ribonucleic acid. It is a type of genetic material, which can act as a messenger (mRNA), that translates information held in DNA into specific proteins.</p>
<p>The concept behind RNA therapies is elegant and simple, in theory. There are two distinct components: the RNA payload and the fatty envelope, made of lipid nanoparticles, which safely delivers the payload to cells. </p>
<p>Once inside a cell, the lipid envelope releases the RNA, enabling it to act as a messenger that will be read and translated to make specific therapeutic proteins. In COVID vaccines, the manufactured protein mirrors the spike protein of the SARS-CoV-2 virus, training our immune system to recognise and remember it for a robust future immune defence.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/messenger-rna-how-it-works-in-nature-and-in-making-vaccines-166975">Messenger RNA: how it works in nature and in making vaccines</a>
</strong>
</em>
</p>
<hr>
<p>It is hard to believe now, but even in the early 2000s RNA therapies were widely considered to be a pipe dream. There were several hurdles in place that, until relatively recently, were considered insurmountable. </p>
<p>Karikó and Weissman’s discovery revolutionised our understanding of how cells detect and react to different RNA structures. </p>
<p>Their discovery allowed therapeutic RNAs to be synthesised so they could avoid destruction by the body before the RNA had a chance to carry out its task. Their <a href="https://www.cell.com/immunity/fulltext/S1074-7613(05)00211-6">seminal paper</a> was published in 2005 – 15 years before the COVID pandemic. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/beyond-covid-vaccines-what-else-could-mrna-technology-do-for-our-health-215142">Beyond COVID vaccines: what else could mRNA technology do for our health?</a>
</strong>
</em>
</p>
<hr>
<h2>Delivering the message</h2>
<p>Throughout this time, a viable delivery system was being developed as well. RNA is a negatively charged, unstable molecule and cannot maintain its structure in the body without some sort of protective casing. </p>
<p>It was only in the 2010s that lipid nanoparticles were developed and identified as a <a href="https://www.nature.com/articles/d41586-021-02483-w">potential mechanism for delivery</a>. </p>
<p>Two critical advancements are essential. First, the lipid nanoparticles are ionised. This allows the encapsulation of the negatively charged RNA with a positively charged envelope. Then, before injection into the body, this assemblage is converted to a neutral pH, reducing potential toxicity in the body.</p>
<p>Second, a method to achieve consistency in the particle size of the lipid nanoparticles was developed. Size consistency matters because it enhances the vaccine’s uptake by cells in the body. </p>
<h2>Time in the spotlight</h2>
<p>By the time the COVID pandemic arrived, the essential components to make a viable RNA vaccine had emerged. RNA vaccines were especially appealing as they can be rapidly synthesised in the lab using just the genetic code of the virus.</p>
<p>As a result, the research field progressed rapidly. In addition to pharmaceutical development, several research groups around the world started work on RNA technology, applying it to a plethora of different diseases, including cancer, gene therapy and vaccines for different infectious diseases.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-do-you-make-a-universal-flu-vaccine-a-microbiologist-explains-the-challenges-and-how-mrna-could-offer-a-promising-solution-195807">How do you make a universal flu vaccine? A microbiologist explains the challenges, and how mRNA could offer a promising solution</a>
</strong>
</em>
</p>
<hr>
<p>However, intellectual property constraints surrounding the lipid nanoparticle envelope raised production costs and affected investment prospects. This meant that while research and design could move forward, taking the findings into the clinic was not possible without paying the premiums to license certain reagents. </p>
<p>The result has been that labs around the world are developing their own techniques from scratch, leading to a grossly inefficient system.</p>
<h2>The democratisation of RNA technology</h2>
<p>Our research expedites the method development process by providing a springboard others can launch off. It is a standardised technique researchers can use as a baseline for RNA therapies without the need for proprietary products. </p>
<p>This will mean more people around the world will be able to bring RNA technology into the clinic, broadening its scope, impact and safety. </p>
<p>Current lipid nanoparticle formulations have also been optimised for a generalised immune defence, rather than specific tissue-targeted immune responses. Unhindered research in this area may unlock findings that allow very specific organs or even cells to be targeted. </p>
<p>It will also enable more universities and even schools to teach and research this technology and improve it for applications beyond those that will be commercially profitable.</p>
<p>We have only seen the tip of the iceberg in terms of the therapeutic potential of RNA technology. By democratising this technology, we can more fully explore and harness its myriad possible therapies.</p>
<hr>
<p><em>The protocol was developed in collaboration with <a href="https://www.wgtn.ac.nz/ferrier">Te Kāuru – Ferrier Research Institute</a> at Te Herenga Waka Victoria University of Wellington.</em> </p>
<hr><img src="https://counter.theconversation.com/content/215704/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This work was supported by funding from New Zealand Ministry of Business Innovation and Employment, Research Trust of Victoria University of Wellington and The Hugh Green Foundation.</span></em></p>Considered a pipe dream not too long ago, research on RNA therapeutics is progressing rapidly. Now a new manufacturing protocol will help researchers to advance the technology.Rebecca McKenzie, Senior Specialist in Molecular Biology, Malaghan Institute of Medical ResearchLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2151422023-10-18T00:33:14Z2023-10-18T00:33:14ZBeyond COVID vaccines: what else could mRNA technology do for our health?<figure><img src="https://images.theconversation.com/files/553619/original/file-20231013-15-yjlqas.jpg?ixlib=rb-1.1.0&rect=0%2C7%2C5000%2C2799&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/single-strand-ribonucleic-acid-rna-molecules-2256712783">nobeastsofierce/Shutterstock</a></span></figcaption></figure><p>Many people first became familiar with the term “<a href="https://www.britannica.com/science/messenger-RNA">mRNA</a>” when Pfizer’s and Moderna’s COVID vaccines were rolled out. In the simplest terms, mRNA, which stands for messenger ribonucleic acid, is a type of genetic material that gives cells in our bodies instructions to make specific proteins.</p>
<p>More recently the 2023 Nobel prize in physiology or medicine was awarded to <a href="https://theconversation.com/nobel-prize-in-medicine-awarded-to-mrna-pioneers-heres-how-their-discovery-was-integral-to-covid-vaccine-development-214763">Katalin Karikó and Drew Weissman</a> from the University of Pennsylvania for their discoveries in mRNA biology.</p>
<p>These scientists’ work has underpinned multiple successful COVID vaccines, which undoubtedly shifted the course of the pandemic. But their discoveries have likewise opened the door to a range of possible therapeutics which, until recently, remained elusive.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/nobel-prize-in-medicine-awarded-to-mrna-pioneers-heres-how-their-discovery-was-integral-to-covid-vaccine-development-214763">Nobel prize in medicine awarded to mRNA pioneers – here's how their discovery was integral to COVID vaccine development</a>
</strong>
</em>
</p>
<hr>
<h2>The promise of mRNA</h2>
<p>Within each of our cells are <a href="https://www.britannica.com/science/ribosome">ribosomes</a>, micro-machines that manufacture proteins, which in turn make up everything from muscle and bone to enzymes and hormones. </p>
<p>mRNA is the intermediate chemical “message” that carries the genetic code locked in the chromosomes of our DNA to the cytoplasm, the fluid that fills our cells and where proteins are made.</p>
<p>The ability to deliver genetic information directly into a cell has been one of medicine’s most obstinate challenges. While mRNA was theoretically the most attractive way to achieve this, it was of little use as a therapy. This is because our immune system mistakes the foreign RNA as being an invading virus, mounting a powerful and toxic immune response. Injecting <a href="https://pubmed.ncbi.nlm.nih.gov/32708595/">naked mRNA</a> therefore can make you very sick.</p>
<p>So it was pivotal when Karakó and Weissman <a href="https://pubmed.ncbi.nlm.nih.gov/16111635/">pioneered a technique</a> to “cloak” mRNA from the immune system, alongside lipid nanoparticles to protect the RNA and allow it to be delivered safely to our cells.</p>
<figure class="align-center ">
<img alt="A health-care worker drawing up a vaccine." src="https://images.theconversation.com/files/553632/original/file-20231013-27-511pl2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/553632/original/file-20231013-27-511pl2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/553632/original/file-20231013-27-511pl2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/553632/original/file-20231013-27-511pl2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/553632/original/file-20231013-27-511pl2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/553632/original/file-20231013-27-511pl2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/553632/original/file-20231013-27-511pl2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">COVID vaccines have shown us the potential of mRNA technology.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-hand-doctor-nurse-laboratory-holding-1949479042">Siyanight/Shutterstock</a></span>
</figcaption>
</figure>
<p>This paved the way for mRNA COVID vaccines which instruct our cells to make spike proteins, proteins on the surface of SARS-CoV-2 (the virus that causes COVID). This is turn primes our immune system to make anti-spike antibodies that then block SARS-CoV-2 from infecting our cells.</p>
<p>Their discovery has opened up new possibilities for how we treat common infectious illnesses as well as genetic diseases that have previously defied treatment.</p>
<h2>Flu vaccines</h2>
<p>Influenza kills up to 650,000 people globally each <a href="https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)">year</a>. At the moment, <a href="https://www.cdc.gov/flu/prevent/vaccine-selection.htm">seasonal vaccines</a> need to be made annually once the main circulating strain has been identified. Manufacture takes about six months, by which time the original flu strain may have evolved. At best the seasonal vaccine is about <a href="https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm">60% effective</a>.</p>
<p>We need a better vaccine and mRNA technology offers the potential of a universal influenza vaccine, with <a href="https://www.pnas.org/doi/full/10.1073/pnas.2123477119">multiple candidates</a> currently undergoing human <a href="https://www.nih.gov/news-events/news-releases/clinical-trial-mrna-universal-influenza-vaccine-candidate-begins">clinical trials</a>. A vaccine, if successful, could replace the current seasonal shots.</p>
<p>The mRNA vaccines are based on a specific part of the influenza protein, called hemagglutinin, teaching the cells to recall it and therefore inducing broad immunity across many influenza strains. In this vaccine, hemagglutinin is the equivalent target the spike protein is in the COVID vaccines.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/3-mrna-vaccines-researchers-are-working-on-that-arent-covid-157858">3 mRNA vaccines researchers are working on (that aren't COVID)</a>
</strong>
</em>
</p>
<hr>
<h2>Cancer treatments</h2>
<p>Targeting cancer is another promising avenue for mRNA technology, with mRNA-based cancer immunotherapies already at the <a href="https://www.nature.com/articles/d41591-023-00072-0">trial stage</a>. </p>
<p>One technique uses mRNA to mimic “neoantigens” (short bits of tumour proteins on the surface of the tumour cells) identified from an individual patient’s tumour cells. Once delivered to the patient’s immune system, their body should produce powerful killer cells called cytotoxic T cells, eliciting a strong anti-tumour immune response.</p>
<figure class="align-center ">
<img alt="A person with a bald head sitting on a bed." src="https://images.theconversation.com/files/553633/original/file-20231013-26-nytgwn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/553633/original/file-20231013-26-nytgwn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/553633/original/file-20231013-26-nytgwn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/553633/original/file-20231013-26-nytgwn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/553633/original/file-20231013-26-nytgwn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/553633/original/file-20231013-26-nytgwn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/553633/original/file-20231013-26-nytgwn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">mRNA technology has a number of possible applications in cancer treatment.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/rear-back-view-stressed-young-hairless-2017483544">fizkes/Shutterstock</a></span>
</figcaption>
</figure>
<p>Chimeric antigen receptor T cells (CAR-T) therapy is a form of <a href="https://www.cancer.gov/about-cancer/treatment/research/car-t-cells">cancer immunotherapy</a> currently in use around the world to treat certain forms of leukaemia. It uses immune cells called T cells that are genetically altered in a lab to help them locate and destroy cancer cells more effectively. </p>
<p>Traditionally CAR-T therapy has required a patient’s T cells to be harvested from white blood cells, modified, and then injected back into the patient. With mRNA technology the time consuming and most expensive steps are <a href="https://www.ornatx.com/our-pipeline/">could be eliminated</a> by delivering the CAR gene directly to T cells in the bloodstream.</p>
<h2>Genetic diseases</h2>
<p>mRNA technology is also transforming our response to some genetic diseases. <a href="https://www.sciencedirect.com/science/article/pii/S1081120622012170">Hereditary angioedema</a> is a rare and potentially fatal genetic disorder where patients suffer severe and repeated attacks of swelling in their organs and tissues. </p>
<p>Scientists had discovered that a specific liver gene called KLKB1 prompts these swelling attacks. Researchers developed mRNA as a system to genetically edit and in turn “silence” the offending gene, with <a href="https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-presents-new-interim-data-first-human">initial results</a> positive for patients.</p>
<p>A similar trial using mRNA to edit the liver gene transthyretin alleviated symptoms in patients suffering a life-threatening hereditary condition called <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2107454">ATTR amyloidosis</a> which affects the nerves and heart.</p>
<h2>The path ahead</h2>
<p>Therapeutics based on mRNA technology are still in their infancy and hurdles remain. For example, mRNA is short-lived in cells and protein is only made for a short time. Increasing the life-span of mRNA in cells would reduce the amount of mRNA required (the dosage). Scientists are working on this and a couple of methods have <a href="https://www.nature.com/articles/d41586-023-03058-7">shown promise</a>. </p>
<p>These caveats aside, the ability to deliver genetic information directly into cells could be a new frontier for medical therapeutics.</p><img src="https://counter.theconversation.com/content/215142/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Fraser receives funding from Health Research Council of New Zealand and the Wellcome Leap R3 Consortium for RNA. </span></em></p>The goal of mRNA technology is to harness the power of the cell to potentially prevent infections and treat diseases.John Fraser, Dean, Faculty of Medical and Health Sciences, University of Auckland, Waipapa Taumata RauLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2147702023-10-03T00:31:22Z2023-10-03T00:31:22ZTenacious curiosity in the lab can lead to a Nobel Prize – mRNA research exemplifies the unpredictable value of basic scientific research<figure><img src="https://images.theconversation.com/files/551551/original/file-20231002-25-ii4mxj.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2100%2C1427&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Basic research often involves lab work that won't be appreciated until decades down the line.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pcr-diagnostics-kit-royalty-free-image/1285418766">Sebastian Condrea/Moment via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://www.nobelprize.org/prizes/medicine/2023/press-release/">2023 Nobel Prize in physiology or medicine</a> will go to Katalin Karikó and Drew Weissman for their discovery that modifying <a href="https://www.genome.gov/genetics-glossary/messenger-rna">mRNA</a> – a form of genetic material your body uses to produce proteins – could reduce unwanted inflammatory responses and allow it to be delivered into cells. While the impact of their findings may not have been apparent at the time of their breakthrough over a decade ago, their work paved the way for the development of the <a href="https://theconversation.com/how-mrna-and-dna-vaccines-could-soon-treat-cancers-hiv-autoimmune-disorders-and-genetic-diseases-170772">Pfizer-BioNTech and Moderna COVID-19 vaccines</a>, as well as many other therapeutic applications currently in development. The <a href="https://www.nobelprize.org/prizes/physics/2023/summary/">2023 Nobel Prize in physics</a> likewise will go to a team of scientists who used lasers to clarify the behavior of electrons, and many prior Nobels have honored basic research.</em></p>
<p><em>We asked André O. Hudson, a <a href="https://scholar.google.com/citations?user=zLwzHqcAAAAJ&hl=en">biochemist and microbiologist</a> at the Rochester Institute of Technology, to explain how basic research like that of this year’s Nobel Prize winners provides the foundations for science – even when its far-reaching effects won’t be felt until years later.</em></p>
<h2>What is basic science?</h2>
<p><a href="https://www.niaid.nih.gov/grants-contracts/basic-research-definition">Basic research</a>, sometimes called fundamental research, is a type of investigation with the overarching goal of understanding natural phenomena like how cells work or how birds can fly. Scientists are asking the fundamental questions of how, why, when, where and if in order to bridge a gap in curiosity and understanding about the natural world.</p>
<p>Researchers sometimes conduct basic research with the hope of eventually developing a technology or drug based on that work. But what many scientists typically do in academia is ask fundamental questions with answers that may or may not ever lead to practical applications.</p>
<p>Humans, and the animal kingdom as a whole, are <a href="https://www.cell.com/current-biology/pdf/S0960-9822(13)00265-0.pdf">wired to be curious</a>. Basic research scratches that itch.</p>
<h2>What are some basic science discoveries that went on to have a big influence on medicine?</h2>
<p>The <a href="https://www.nobelprize.org/prizes/medicine/2023/press-release/">2023 Nobel Prize in physiology or medicine</a> acknowledges basic science work done in the early 2000s. Karikó and Weissman’s discovery about modifying mRNA to reduce the body’s inflammatory response to it allowed other researchers to leverage it to make improved vaccines.</p>
<p>Another example is the <a href="https://theconversation.com/guns-not-roses-heres-the-true-story-of-penicillins-first-patient-178463">discovery of antibiotics</a>, which was based on an unexpected observation. In the late 1920s, the microbiologist Alexander Fleming was growing a species of bacteria in his lab and found that his Petri dish was accidentally contaminated with the fungus <em>Penicillium notatum</em>. He noticed that wherever the fungus was growing, it impeded or inhibited the growth of the bacteria. He wondered why that was happening and subsequently went on to isolate penicillin, which was approved for medical use in the early 1940s.</p>
<p>This work fed into more questions that ushered in the age of antibiotics. The 1952 Nobel Prize in physiology or medicine was awarded to Selman Waksman for his <a href="https://www.nobelprize.org/prizes/medicine/1952/summary/">discovery of streptomycin</a>, the first antibiotic to treat tuberculosis.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/CNbnLgetqHs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Penicillin was discovered by accident.</span></figcaption>
</figure>
<p>Basic research often involves seeing something surprising, wanting to understand why and deciding to investigate further. Early discoveries start from a basic observation, asking the simple question of “How?” Only later are they parlayed into a medical technology that helps humanity.</p>
<h2>Why does it take so long to get from curiosity-driven basic science to a new product or technology?</h2>
<p>The mRNA modification discovery could be considered to be on a relatively fast track from basic science to application. Less than 15 years passed between Karikó and Weissman’s findings and the COVID-19 vaccines. The importance of their discovery came to the forefront with the pandemic and the <a href="https://www.commonwealthfund.org/blog/2022/two-years-covid-vaccines-prevented-millions-deaths-hospitalizations">millions of lives</a> they saved.</p>
<p>Most basic research won’t reach the market until <a href="https://doi.org/10.1126/scitranslmed.aaa0599">several decades</a> after its initial publication in a science journal. One reason is because it depends on need. For example, <a href="https://www.fda.gov/drugs/information-consumers-and-patients-drugs/orphan-products-hope-people-rare-diseases">orphan diseases</a> that affect only a small number of people will get less attention and funding than conditions that are ubiquitous in a population, like cancer or diabetes. Companies don’t want to spend billions of dollars developing a drug that will only have a small return on their investment. Likewise, because the return on investment for basic research often isn’t clear, it can be a hard sell to support financially.</p>
<p>Another reason is cultural. Scientists are trained to chase after funding and support for their work wherever they can find it. But sometimes that’s not as easy as it seems.</p>
<p>A good example of this was when the <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">human genome was first sequenced</a> in the early 2000s. A lot of people thought that having access to the full sequence would lead to treatments and cures for many different diseases. <a href="https://theconversation.com/why-sequencing-the-human-genome-failed-to-produce-big-breakthroughs-in-disease-130568">But that has not been the case</a>, because there are many nuances to translating basic research to the clinic. What works in a cell or an animal might not translate into people. There are many steps and layers in the process to get there.</p>
<h2>Why is basic science important?</h2>
<p>For me, the most critical reason is that basic research is how we <a href="https://dx.doi.org/10.1210%2Fme.2014-1343">train and mentor future scientists</a>. </p>
<p>In an academic setting, telling students “Let’s go develop an mRNA vaccine” versus “How does mRNA work in the body” influences how they approach science. How do they design experiments? Do they start the study going forward or backward? Are they argumentative or cautious in how they present their findings?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of scientist wearing nitrile gloves looking into microscope hovering over Petri dish" src="https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There are many steps between translating findings in a lab to the clinic.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/scrutinising-a-new-sample-royalty-free-image/1206157642">Marco VDM/E+ via Getty Images</a></span>
</figcaption>
</figure>
<p>Almost every scientist is trained under a basic research umbrella of how to ask questions and go through the scientific method. You need to understand how, when and where mRNAs are modified before you can even begin to develop an mRNA vaccine. I believe the best way to inspire future scientists is to encourage them to expand on their curiosity in order to make a difference. </p>
<p>When I was writing my dissertation, I was relying on studies that were published in the late 1800s and early 1900s. Many of these studies are still cited in scientific articles today. When researchers share their work, though it may not be today or tomorrow, or 10 to 20 years from now, it will be of use to someone else in the future. You’ll make a future scientist’s job a little bit easier, and I believe that’s a great legacy to have.</p>
<h2>What is a common misconception about basic science?</h2>
<p>Because any immediate use for basic science can be very hard to see, it’s easy to think this kind of research <a href="https://theconversation.com/funding-basic-research-plays-the-long-game-for-future-payoffs-100435">is a waste of money or time</a>. Why are scientists breeding mosquitoes in these labs? Or why are researchers studying migratory birds? The same argument has been made with astronomy. Why are we spending billions of dollars putting things into space? Why are we looking to the edge of the universe and studying stars when they are millions and billions of light years away? How does it affect us?</p>
<p>There is a need for <a href="https://doi.org/10.1073/pnas.1912436117">more scientific literacy</a> because not having it can make it difficult to understand why basic research is necessary to future breakthroughs that will have a major effect on society.</p>
<p>In the short term, the worth of basic research can be hard to see. But in the long term, history has shown that a lot of what we take for granted now, such as common medical equipment like <a href="https://www.aps.org/publications/apsnews/200111/history.cfm">X-rays</a>, <a href="https://nationalmaglab.org/magnet-academy/history-of-electricity-magnetism/pioneers/theodore-maiman/">lasers</a> and <a href="https://www.aps.org/publications/apsnews/200607/history.cfm">MRIs</a>, came from basic things people discovered in the lab. </p>
<p>And it still goes down to the fundamental questions – we’re a species that seeks answers to things we don’t know. As long as curiosity is a part of humanity, we’re always going to be seeking answers.</p><img src="https://counter.theconversation.com/content/214770/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>André O. Hudson receives funding from the National Institutes of Health. </span></em></p>The winners of the 2023 Nobel Prize in physiology or medicine made a discovery that helped create the COVID-19 vaccines. They couldn’t have anticipated the tremendous impact of their findings.André O. Hudson, Dean of the College of Science, Professor of Biochemistry, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2147632023-10-02T15:57:01Z2023-10-02T15:57:01ZNobel prize in medicine awarded to mRNA pioneers – here’s how their discovery was integral to COVID vaccine development<p>Billions of people around the world have received the Pfizer or Moderna COVID-19 vaccines. The rapid development of these vaccines changed the course of the pandemic, providing protection against the SARS-CoV-2 virus. </p>
<p>But these vaccines would not have been possible it if weren’t for the pioneering work of <a href="https://www.nobelprize.org/prizes/medicine/2023/press-release/">this year’s winners</a> of the Nobel prize in physiology or medicine decades earlier.</p>
<p>Dr Katalin Karikó and Dr Drew Weissman, researchers from the University of Pennsylvania, have been given the prestigious award for their discoveries into mRNA biology. The pair were the first to discover a way of modifying mRNA that allowed it to successfully be delivered to cells and replicated by them. </p>
<p>Their discovery was not only integral to COVID-19 vaccine development, but may also lead to the development of many other therapies – such as vaccines for cancer.</p>
<h2>Life’s work</h2>
<p>Karikó is a Hungarian biochemist and Weissman an American physician scientist. The two began working together in 1985 when Karikó was a postdoctoral researcher at the University of Pennsylvania, where Weissman was already working as an immunologist. They had a shared interest in how mRNA could be used to make new therapies. </p>
<p>Messenger RNA (better known as mRNA) is an essential molecule to life. It’s made in the body from our very own DNA in a process called translation. DNA is our special encoded handbook of instructions for manufacturing proteins, which are the building blocks for material in the body. </p>
<p>Our mRNA copies and carries these genetic instructions from our DNA to our cells. The cells then make whatever protein they’ve been instructed to, such as haemoglobin which helps red blood cells carry oxygen around the body.</p>
<p>Karikó and Weissman thought that if it was possible to commandeer this process, mRNA could be used to instruct cells to essentially make their own cures. But at the time they started working together, attempts by other researchers to do this had been unsuccessful.</p>
<p>The researchers faced two major challenges as they began their work. The first was being able to prevent the host from mounting an immune response against the modified mRNA. The second was being able to deliver the mRNA into the host safely without it degrading.</p>
<p>To understand how they overcame the first barrier, it’s important to understand mRNA’s structure. Normally, mRNA molecules contain four types of smaller molecules known as bases (nucleosides): A (adenine), U (uridine), G (guanine), and C (cytosine). Different sequences of these bases can be strung together to produce the basis of an mRNA molecule.</p>
<figure class="align-center ">
<img alt="A digital illustration of a strand of mRNA." src="https://images.theconversation.com/files/551466/original/file-20231002-19-lxrhms.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551466/original/file-20231002-19-lxrhms.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551466/original/file-20231002-19-lxrhms.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551466/original/file-20231002-19-lxrhms.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551466/original/file-20231002-19-lxrhms.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551466/original/file-20231002-19-lxrhms.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551466/original/file-20231002-19-lxrhms.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Messenger RNA copies and carries genetic instructions from our DNA.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/molecular-model-messenger-ribonucleic-acid-mrna-2205462601">Kateryna Kon/ Shutterstock</a></span>
</figcaption>
</figure>
<p>In early experiments, Karikó and Weismann found that injecting normal mRNA molecules into mice led to an immune response. This meant the mouse’s immune system saw the new mRNA as an invading pathogen and the immune cells would destroy it, instead of replicating it.</p>
<p>So the <a href="https://www.nature.com/articles/s41577-021-00608-w">researchers modified</a> the U nucleoside to create a pseudouridine, a chemical compound which stabilises RNA’s structure. When they repeated their experiment with the modified mRNA, the mice exhibited <a href="https://www.cell.com/immunity/fulltext/S1074-7613(05)00211-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761305002116%3Fshowall%3Dtrue">no immune response</a>.</p>
<p>But Karikó and Weismann still faced the second challenge of being able to deliver the bespoke mRNA without it degrading. </p>
<p>They decided to use lipids (a nanoparticle) to deliver it. These fatty chemical compounds are an essential part of the cell membrane, controlling what enters and leaves the cell. Specially created lipids allowed the mRNA molecules <a href="https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)32681-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1525001616326818%3Fshowall%3Dtrue">to be delivered</a> without being degraded or broken down by the immune system. </p>
<p>Karikó and Weissman’s research had successfully eliminated the obstacles that had previously stood in the way of using mRNA clinically. Being able to instruct the body to replicate virtually any harmless protein could have potential for treating a range of diseases and even protect against viral infections.</p>
<h2>COVID vaccines</h2>
<p>When their research was first published, it didn’t garner <a href="https://www.nytimes.com/2023/10/02/health/nobel-prize-medicine.html#:%7E:text=Katalin%20Karik%C3%B3%20and%20Drew%20Weissman%2C%20who%20together%20identified%20a%20chemical,Physiology%20or%20Medicine%20on%20Monday.">much attention</a>. But in 2011, two biotech companies – Moderna and BioNTech – took notice and began research into mRNA medicines.</p>
<p>It’s no wonder why. Traditional vaccine production methods are time consuming, expensive and don’t work for every vaccine. But Karikó and Weissman’s work showed that synthetic mRNA could be made at a large scale. </p>
<p>Researchers had already been working on developing mRNA vaccines before the pandemic, such as a <a href="https://www.nature.com/articles/d41586-022-03590-y#:%7E:text=There%20is%20some%20research%20suggesting,immune%20responses%20in%20guinea%20pigs.">vaccine for Ebola</a> that didn’t receive much commercial interest. But in 2020, when COVID-19 began spreading around the globe, vaccines were needed quickly to offer protection.</p>
<p>Using the foundational work of Karikó and Weissman, scientists developed a bespoke mRNA sequence which mimicked the spike protein (which allows the virus to enter our cells). This produced a harmless COVID particle which our cells then replicated, allowing our bodies to protect us from severe COVID infections when it encountered the real virus.</p>
<p>Karikó and Weissman’s discoveries years earlier were critical in making the COVID-19 mRNA vaccines possible. But these aren’t the only ways their work could be applied. </p>
<p>Researchers are now hoping to develop mRNA vaccines for diseases such as HIV and Zika virus. Studies have also shown mRNA vaccines might be useful in treating <a href="https://theconversation.com/pancreatic-cancer-a-personalised-mrna-vaccine-may-boost-effects-of-treatment-205606">certain types of cancer</a>.</p><img src="https://counter.theconversation.com/content/214763/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alice Godden does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The prestigious prize was awarded to Dr Katalin Karikó and Dr Drew Weissman from the University of Pennsylvania.Alice Godden, Senior research associate, School of Biological Sciences, University of East AngliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2056062023-05-19T14:52:44Z2023-05-19T14:52:44ZPancreatic cancer: a personalised mRNA vaccine may boost effects of treatment<figure><img src="https://images.theconversation.com/files/527196/original/file-20230519-27-z54c2x.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5991%2C3988&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Immunotherapies, such as cancer vaccines, help train the immune system to fight off cancer.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-doctors-hand-purple-gloves-holding-1788967661">Pand P Studio/ Shutterstock</a></span></figcaption></figure><p>Pancreatic cancer is one of the <a href="https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer#heading-One">deadliest types of cancer</a>. This is largely due to the fact that pancreatic cancer symptoms typically don’t arise until the late stages of the disease, making many patients ineligible for the current best treatment method, which is surgery to remove any tumours. </p>
<p>Even in patients who have tumours removed, there’s often a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679234">really high chance</a> of the cancer returning.</p>
<p>But the results of a recent study suggest that the immune system could be a useful tool in treating pancreatic cancer. The research, which was published in <a href="https://www.nature.com/articles/s41586-023-06063-y">Nature</a>, showed a personalised cancer vaccine was able to stimulate the immune system in half of the patients who received it. </p>
<p>This heightened immune response was also still detectable in these patients a year and a half later.</p>
<p>In order to understand how this pancreatic cancer vaccine works, it’s important to first understand the role that the immune system plays in preventing cancer.</p>
<p>Our immune system is often very well equipped to fight cancer. But unfortunately, cancer cells contain certain protein receptors whose purpose is to help them hide from our immune cells – effectively preventing our immune system from destroying them. </p>
<p>However, scientists have found a way to block these receptors, so the immune system is able to recognise cancer cells as a threat again and remove them.</p>
<p>This is what <a href="https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/what-is-immunotherapy.html">immunotherapy</a> – one of the newest techniques for treating cancer – does. These therapies work by harnessing the power of the immune system.</p>
<p>There are a few different types of immunotherapies, but a new one that is promising against cancer is the use of mRNA vaccines. These use genetic material in order to stimulate the immune system.</p>
<p>Scientists first begin by taking the genetic material of cancer cells and identifying the most mutated parts of the DNA – so-called neoantigens – before putting them in between a strand of mRNA. </p>
<p>If we think of DNA as the hard drive, mRNA is sort of like the software of our cells. It’s function is essentially to copy and carry genetic instructions from our DNA to other parts of the cell.</p>
<p>This mRNA is then given to patients as a personalised vaccine. It’s personalised because everyone has different neoantigens, so everyone receives slightly different vaccines with slightly different mutations encoded into the mRNA strand. </p>
<p>Once injected into the patient, the mRNA then makes a little bit of the cancer – just enough to stimulate the immune system. The idea is that the person’s immune systems will then react to the cancer and give them protection.</p>
<p>This is how the recent pancreatic cancer mRNA vaccine was developed. The pharmaceutical company BioNtech created personalised mRNA vaccines for 16 participants using cells from their recently removed tumours.</p>
<figure class="align-center ">
<img alt="A digital drawing of T cells attacking a cancer cell." src="https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/527194/original/file-20230519-15-w4pjjb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Half of the participants had an increase in T cell levels.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/tcells-work-fight-cancer-immunotherapy-car-1972711475">Design_Cells/ Shutterstock</a></span>
</figcaption>
</figure>
<p>The patients were all treated with this personalised vaccine, alongside another form of immunotherapy (the drug atezolizumab) followed by aggressive chemotherapy. </p>
<p>Half of the patients treated with the vaccine and immunotherapy combination saw an increase in a specific type of immune cell (called a T cell, which is known to protect against cancer). This showed the researchers that for at least some participants, their immune systems might be learning to fight the cancer.</p>
<p>At an 18-month follow-up, the patients who’d seen the increase in T cells still had signs of improved immune response. Most also had no signs of their cancer recurring. </p>
<p>The authors concluded that it may be because the immune system was successfully stimulated which helped stop the cancer returning. The mRNA vaccine was also well tolerated by patients with no obvious major side effects.</p>
<h2>Immune function</h2>
<p>While this trial’s findings are intriguing, its numbers are too small to draw any major conclusions. It will be necessary for larger trials to be conducted including randomised studies. </p>
<p>This would see only some of the participants receive the vaccine, allowing researchers to truly understand what effect it has – and whether the vaccine really does what it’s supposed to do, which is stimulate the immune system and improve time before recurrence (and ultimately survival). </p>
<p>This would also allow them to see whether the vaccine had a distinct effect, and that this effect wasn’t just down to the other treatments or immunotherapy the participants received.</p>
<p>It’s promising to see that we may have a new type of therapy to investigate for treating pancreatic cancer. These findings also highlight the potential of mRNA vaccines as a cancer treatment more broadly – building on the results of another study from last year which showed an mRNA vaccine to be <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/moderna-merck-vaccine-combo-cut-melanoma-recurrence-by-44-study-2022-12-13/">effective against melanoma</a>.</p><img src="https://counter.theconversation.com/content/205606/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Justin Stebbing is editor-in-chief of Oncogene. His conflicts are listed here and none are relevant to this piece:
<a href="https://www.nature.com/onc/editors">https://www.nature.com/onc/editors</a></span></em></p>This study further highlights the potential of mRNA vaccines in cancer treatment.Justin Stebbing, Professor of Biomedical Sciences, Anglia Ruskin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2047742023-05-17T12:40:51Z2023-05-17T12:40:51ZVaccines using mRNA can protect farm animals against diseases traditional ones may not – and there are safeguards to ensure they won’t end up in your food<figure><img src="https://images.theconversation.com/files/525981/original/file-20230512-28-6v7puj.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3008%2C2008&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Vaccines help protect farm animals from various diseases.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/veterinarian-and-pigs-royalty-free-image/512631046">dusanpetkovic/iStock via Getty Images Plus</a></span></figcaption></figure><p>While effective vaccines for COVID-19 should have heralded the benefits of mRNA vaccines, <a href="https://theconversation.com/misinformation-is-a-common-thread-between-the-covid-19-and-hiv-aids-pandemics-with-deadly-consequences-187968">fear and misinformation</a> about their supposed dangers circulated at the same time. These misconceptions about mRNA vaccines have recently spilled over into worries about whether their use in agricultural animals could expose people to components of the vaccine <a href="https://www.usatoday.com/story/news/factcheck/2023/02/15/fact-check-false-claim-mrna-vaccines-food-supply/11218991002/">within animal products</a> such as meat or milk.</p>
<p>In fact, a number of states are drafting or considering legislation outlawing the use of mRNA vaccines in food animals or, at minimum, requiring their labeling on animal products in grocery stores. <a href="https://legislature.idaho.gov/sessioninfo/2023/legislation/H0154/">Idaho introduced a bill</a> that would make it a misdemeanor to administer any type of mRNA vaccine to any person or mammal, including COVID-19 vaccines. A <a href="https://www.house.mo.gov/Bill.aspx?bill=HB1169&year=2023&code=R">Missouri bill</a> would have required the labeling of animal products derived from animals administered mRNA vaccines but failed to get out of committee. <a href="https://www.azleg.gov/legtext/56leg/1R/summary/H.HB2762_020823_LARA.DOCX.htm">Arizona</a> and <a href="https://wapp.capitol.tn.gov/apps/BillInfo/Default.aspx?BillNumber=SB0099&GA=113">Tennessee</a> have also proposed labeling bills. <a href="https://www.oklahomafarmreport.com/okfr/2023/04/21/mike-deering-corrects-false-accusations-of-cattle-industry-using-mrna-vaccines/">Several other</a> <a href="https://www.texasagriculture.gov/News-Events/Article/7596/Commissioner-Miller-Statement-on-mRNA-Vaccines-in-Livestock">state legislatures</a> are discussing similar measures.</p>
<p>I am a <a href="https://scholar.google.com/citations?user=yTZZQ3QAAAAJ&hl=en">researcher who has been making vaccines</a> for a number of years, and I started studying mRNA vaccines before the pandemic started. My research on using <a href="https://portal.nifa.usda.gov/web/crisprojectpages/1027610-novel-mrna-vaccine-technology-for-prevention-of-bovine-respiratory-syncytial-virus.html">mRNA vaccines for cattle respiratory viruses</a> has been referenced by social media users and anti-vaccine activists who say that using these vaccines in animals will endanger the health of people who eat them.</p>
<p>But these vaccines have been shown to reduce disease on farms, and it’s all but impossible for them to end up in your food.</p>
<h2>Traditional animal vaccine approaches</h2>
<p>In food animals, <a href="https://www.merckvetmanual.com/pharmacology/vaccines-and-immunotherapy/types-of-vaccines-for-animals">several types of vaccines</a> have long been available for farmers to protect their animals from common diseases. These include inactivated vaccines that contain a killed version of a pathogen, live attenuated vaccines that contain a weakened version of a pathogen and subunit vaccines that contain one part of a pathogen. All can elicit good levels of protection from disease symptoms and infection. Producing these vaccines is <a href="https://pubmed.ncbi.nlm.nih.gov/17892154/">often inexpensive</a>.</p>
<p>However, each of these vaccines <a href="https://doi.org/10.1007%2F978-1-4939-3389-1_1">has drawbacks</a>. </p>
<p>Inactivated and subunit vaccines often do not produce a strong enough immune response, and pathogens can quickly mutate into variants that <a href="https://doi.org/10.3389/fvets.2021.697839">limit vaccine effectiveness</a>. The weakened pathogens in live attenuated vaccines have the remote possibility of <a href="https://doi.org/10.1093%2Fve%2Fvev005">reverting back</a> to their full pathogenic form or mixing with other circulating pathogens and becoming new vaccine-resistant ones. They also must be grown in specific cell cultures to produce them, which can be time-consuming.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/mvA9gs5gxNY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Each type of vaccine has pros and cons.</span></figcaption>
</figure>
<p>There are also <a href="https://doi.org/10.1186/s13567-018-0560-8">several pathogens</a> – such as porcine reproductive and respiratory syndrome virus, foot and mouth disease virus, <a href="https://theconversation.com/bird-flu-is-killing-millions-of-chickens-and-turkeys-across-the-us-180299">H5N1 influenza</a> and African swine fever virus – for which all three traditional approaches have yet to yield an effective vaccine.</p>
<p>Another major drawback for all three of these vaccine types is the <a href="https://doi.org/10.1016%2Fj.tvjl.2007.11.009">time it takes</a> to test and obtain federal approval to use them. Typically, animal vaccines take <a href="https://doi.org/10.1016%2Fj.vaccine.2020.05.007">three or more years</a> from development to licensure by the U.S. Department of Agriculture. Should new viruses make it to farms, playing catch-up using traditional vaccines could take too long to contain an outbreak. </p>
<h2>Advantages of animal mRNA vaccines</h2>
<p>All cells use <a href="https://theconversation.com/what-is-mrna-the-messenger-molecule-thats-been-in-every-living-cell-for-billions-of-years-is-the-key-ingredient-in-some-covid-19-vaccines-158511">mRNA, which contains the instructions</a> to make the proteins needed to carry out specific functions. The mRNA used in vaccines encode instructions to make a protein from a pathogen of interest that immune cells learn to recognize and attack. This process builds <a href="https://theconversation.com/how-long-does-protective-immunity-against-covid-19-last-after-infection-or-vaccination-two-immunologists-explain-177309">immunological memory</a>, so that when a pathogen carrying that same protein enters the body, the immune system will be ready to mount a quick and strong response against it.</p>
<p>Compared to traditional vaccines, mRNA vaccines have several advantages that make them ideal for protecting people and farm animals from both emerging and persistent diseases.</p>
<p>Unlike killed or subunit vaccines, mRNA vaccines increase the buildup of vaccine proteins in cells over time and train the immune system using conditions that look more like a viral infection. Like live attenuated vaccines, this process fosters the development of <a href="https://medicine.wustl.edu/news/what-makes-an-mrna-vaccine-so-effective-against-severe-covid-19/">strong immune responses</a> that may build better protection. In contrast to live attenuated viruses, mRNA vaccines cannot revert to a pathogenic form or mix with circulating pathogens. Furthermore, once the genetic sequence of a pathogen of interest is known, mRNA vaccines can be <a href="https://www.businessinsider.com/moderna-designed-coronavirus-vaccine-in-2-days-2020-11/">produced rather quickly</a>.</p>
<p>The mRNA in vaccines can come in either a form that is structurally similar to what is normally found in the body, like those used in COVID-19 vaccines for people, or in a form that is <a href="https://doi.org/10.1038/s41434-020-00204-y?">self-amplifying, called saRNA</a>. Because saRNA allows for higher levels of protein synthesis, researchers think that less mRNA would be needed to generate similar levels of immunity. However, a COVID-19 saRNA vaccine for people developed <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/curevac-covid-19-vaccine-records-only-48-efficacy-final-trial-readout-2021-06-30/#">by biopharmaceutical company CureVac</a> elicited less protection than traditional mRNA approaches.</p>
<p><a href="https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinary-biologics/product-summaries/Vet-Label-Data/d611b51a-9eca-4d56-9556-dcc61fb96d5f">Merck’s Sequivity</a> is currently the only saRNA vaccine licensed for use in animals, and it is available by prescription to protect against swine flu in pigs.</p>
<h2>Persistance of mRNA vaccine components</h2>
<p>All mRNA vaccines are made in the laboratory using methods that were <a href="https://publichealth.jhu.edu/2021/the-long-history-of-mrna-vaccines">developed decades ago</a>. Only recently has the technology advanced to the point where the body doesn’t immediately reject it by activating the antiviral defenses intrinsic to each of your cells. This rejection would occur before the immune system even had the chance to mount a response.</p>
<p>The COVID-19 mRNA vaccines used in people <a href="https://doi.org/10.1021/acscentsci.1c00197">mix in modified nucleotides</a> – the building blocks of RNA – with unmodified nucleotides so the mRNA can hide from the intrinsic antiviral sensors of the cell. These modified nucleotides are what allow the mRNA to persist in the body’s cells <a href="https://theconversation.com/no-covid-vaccines-dont-stay-in-your-body-for-years-169247">for a few days</a> rather than <a href="https://doi.org/10.1016/0022-2836(73)90119-8">just a few hours</a> like natural mRNAs.</p>
<p>New methods of delivering the vaccine using <a href="https://theconversation.com/nanoparticles-are-the-future-of-medicine-researchers-are-experimenting-with-new-ways-to-design-tiny-particle-treatments-for-cancer-180009">lipid nanoparticles</a> also ensure the mRNA isn’t degraded before it has a chance to enter cells and start making proteins.</p>
<p>Despite this stability, mRNA vaccines do not last long enough within animals after injection for any component of the vaccine to end up on grocery store shelves. Unlike for human vaccines, animal vaccine manufacturers must determine the <a href="https://www.aphis.usda.gov/animal_health/vet_biologics/publications/pel_4_9.pdf">withdrawal period</a> in order to obtain USDA approval. This means any component of a vaccine cannot be found in the animal prior to milking or slaughter. Given the short lifespan of some of the agriculture animals and intensive milking schedules, withdrawal periods often need to be very short.</p>
<p>Between the mandatory vaccine withdrawal period, flash pasteurization for milk, degradation on the shelf and the cooking process for food products, there could not be any residual vaccine left for humans to consume. Even if you were to consume residual mRNA molecules, your gastrointestinal tract will <a href="https://doi.org/10.1016/j.matt.2021.12.022">rapidly degrade them</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/525996/original/file-20230512-24902-28dwi7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Dairy cows lined up for milking" src="https://images.theconversation.com/files/525996/original/file-20230512-24902-28dwi7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/525996/original/file-20230512-24902-28dwi7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/525996/original/file-20230512-24902-28dwi7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/525996/original/file-20230512-24902-28dwi7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/525996/original/file-20230512-24902-28dwi7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/525996/original/file-20230512-24902-28dwi7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/525996/original/file-20230512-24902-28dwi7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Withdrawal periods are intended to ensure no component of the vaccine is present in the animal’s body before milking or slaughter.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/dairy-cows-ready-for-milking-royalty-free-image/1267197465">kolderal/Moment via Getty Images</a></span>
</figcaption>
</figure>
<p>Several mRNA vaccines for use in animals <a href="https://portal.nifa.usda.gov/web/crisprojectpages/1027610-novel-mrna-vaccine-technology-for-prevention-of-bovine-respiratory-syncytial-virus.html">are in</a> <a href="https://www.genengnews.com/topics/drug-discovery/bayer-partners-with-biontech-to-develop-mrna-vaccines-drugs-for-animal-health/">early stages</a> <a href="https://www.porkbusiness.com/news/industry/genvax-technologies-secures-65-million-advance-novel-vaccine-platform">of development</a>. Merck’s USDA-licensed Sequivity does not use the modified nucleotides or lipid nanoparticles that allow those vaccine components to circulate for slightly longer periods in the body, so long-term persistence is unlikely.</p>
<p>Like in people, animal vaccines are <a href="https://www.aphis.usda.gov/animal_health/vet_biologics/publications/memo_800_202.pdf">tested for their safety and effectiveness</a> in clinical trials. Approval for use from the <a href="https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinary-biologics/CT_Vb_licensed_products">USDA Center for Vaccine Biologics</a> requires a modest level of protection against infection or disease symptoms. As with all animal vaccines, future mRNA vaccines will also need to be fully cleared from the animal’s body before they can be used in animals for human consumption.</p>
<h2>mRNA vaccines for more farm animals</h2>
<p>Whether mRNA vaccines will displace other vaccine types for livestock is yet to be determined. The <a href="https://www.kff.org/coronavirus-covid-19/issue-brief/how-much-could-covid-19-vaccines-cost-the-u-s-after-commercialization/">cost of manufacturing these vaccines</a>, their need to <a href="https://www.vox.com/21552934/moderna-pfizer-covid-19-vaccine-biontech-coronavirus-cold-chain">kept very cold and warm up before use</a> to avoid degradation, and the efficacy of different types of mRNA vaccines all still need to be addressed before large-scale use can take place. </p>
<p>Traditional vaccines for food animals have <a href="https://pressbooks.umn.edu/vetprevmed/chapter/chapter-4-vaccines-and-vaccinations-production/">protected them against many diseases</a>. Limiting the use of mRNA vaccines right now would mean losing a new way to protect animals from pesky pathogens that current vaccines can’t fend off.</p><img src="https://counter.theconversation.com/content/204774/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Verhoeven received funding from Merck and USDA. Those funding are now expired.</span></em></p>While mRNA vaccines are designed to last longer in the body than mRNA molecules typically would, they are also tested to ensure they are eliminated from livestock long before milking or slaughter.David Verhoeven, Assistant Professor of Vet Microbiology and Preventive Medicine, Iowa State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1979882023-03-06T19:03:37Z2023-03-06T19:03:37ZWhat are these ‘cancer vaccines’ I’m hearing about? And what similarities do they share with COVID vaccines?<figure><img src="https://images.theconversation.com/files/512847/original/file-20230301-26-rrwmap.jpg?ixlib=rb-1.1.0&rect=146%2C77%2C5604%2C3750&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/closeup-portrait-young-scientist-labcoat-wearing-199443881">Shutterstock</a></span></figcaption></figure><p>Barely a month goes by without headlines announcing yet another advancement in cancer vaccines. </p>
<p>Just last month, the United States Food and Drug Administration (FDA) <a href="https://www.pharmtech.com/view/investigational-personalized-mrna-cancer-vaccine-gains-breakthrough-therapy-designation-from-fda">granted</a> breakthrough therapy designation to Moderna and Merck’s skin cancer vaccine. This allows expedited development and review of drugs intended to treat serious conditions.</p>
<p>We already have a <a href="https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/what-are-cancer-vaccines#:%7E:text=Are%20there%20vaccines%20that%20treat,immune%20system%20to%20fight%20cancer.">vaccine</a> to prevent human papillomavirus (HPV), which causes cervical and other cancers. We also have a vaccine to protect against the hepatitis B virus, which can cause liver cancer.</p>
<p>But you may have heard of new types of cancer vaccines being developed using technology similar to that used for COVID vaccines. Decades before COVID vaccines, scientists had been working on messenger ribonucleic acid (mRNA) vaccines targeting cancer. </p>
<p>Rather than preventing disease, these vaccines are a personalised treatment for cancer, to combat disease. </p>
<h2>How do they work?</h2>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/zL1l8PpAJJg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Science in Motion.</span></figcaption>
</figure>
<p>Traditionally, vaccines inject part or all of a weakened virus (or other pathogen) into the body to provoke an immune response. </p>
<p>mRNA <a href="https://pharmaceutical-journal.com/article/feature/how-close-are-we-to-developing-an-mrna-cancer-vaccine">works by</a> injecting only the genetic instructions and allowing the body’s cells to make part of the cancer protein (antigen) itself. This trains the immune system to develop antibodies against the protein. </p>
<p>When these same proteins are present on an invading tumour cell, the immune system stimulates an immune response against it. </p>
<p>While COVID mRNA vaccines respond to one antigen – the spike protein on the outside of coronavirus – cancer vaccines act on several antigens present on the tumour surface. </p>
<p>The mRNA cancer vaccines train the patient’s immune system to fight their own cancer. Most <a href="https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00372-2/fulltext">trials</a> are manufacturing vaccines for individual patients based on the specific antigens present on their tumours. </p>
<p>It takes around <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer">two months</a> to produce a vaccine.</p>
<figure class="align-center ">
<img alt="Doctor checks patient's mole" src="https://images.theconversation.com/files/512850/original/file-20230301-26-3mtp2i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/512850/original/file-20230301-26-3mtp2i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=384&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512850/original/file-20230301-26-3mtp2i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=384&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512850/original/file-20230301-26-3mtp2i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=384&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512850/original/file-20230301-26-3mtp2i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=482&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512850/original/file-20230301-26-3mtp2i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=482&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512850/original/file-20230301-26-3mtp2i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=482&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The vaccine stimulates an immune response against cancer cells.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/dermatologist-examines-moles-acne-patient-dermatoscope-784036480">Shutterstock</a></span>
</figcaption>
</figure>
<h2>How are they made?</h2>
<p>To <a href="https://www.europeanpharmaceuticalreview.com/news/177505/mrna-vaccine-plus-keytruda-improve-melanoma-survival/">make these vaccines</a>, a sample of the patient’s tumour and healthy tissue is taken. These samples are DNA-sequenced to compare differences between the DNA in the cancerous cells and the healthy cells. </p>
<p>Scientists identify problem mutations driving disease. These can then be used as antigen targets in the mRNA vaccine. </p>
<p>Bespoke approaches allow scientists to target a wider range of cancer antigens. Targeting multiple antigens decreases the odds that cancer cells will mutate and become resistant to vaccines, because the immune system attacks on multiple fronts.</p>
<p>Personalised medicines are <a href="https://www.health.gov.au/ministers/the-hon-greg-hunt-mp/media/expanded-access-to-cutting-edge-car-t-cell-therapy">extremely expensive</a> because they are bespoke products. Manufacturing costs for bespoke treatments remain high. However, with rapidly falling costs of different aspects such as genome sequencing (some companies are now offering genome sequencing for just <a href="https://leaps.org/genome/">US$100</a>), sequencing the entire genome is becoming more viable. </p>
<p>As large-scale manufacturing increases in future for off-the-shelf vaccines, there will be resource efficiencies that reduce cost. </p>
<h2>What vaccines are in development?</h2>
<p>In December 2022, Moderna and Merck (known outside the United States and Canada as <a href="https://www.biopharma-reporter.com/Article/2022/12/13/Moderna-s-vaccine-combined-with-Keytruda-reduced-melanoma-recurrence-by-44-The-results-are-highly-encouraging-for-the-field-of-cancer-treatment">MSD</a>) published the results of its early phase (2b) <a href="https://www.bbc.com/news/health-63959843">clinical trial</a>. The trial was investigating a combination therapy of an mRNA vaccine and immunotherapy (a drug that stimulates an immune response) in advanced stage melanoma patients. </p>
<p>After one year of treatment in 157 patients, they found the combination reduced the risk of <a href="https://www.theguardian.com/science/2023/jan/22/the-other-big-c-how-the-science-behind-covid-vaccines-might-help-to-fight-cancer">cancer recurrence or death by 44%</a>. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1630130831011336192"}"></div></p>
<p>Now, Moderna and Merck plan to follow up their initial trial with a phase 3 trial for advanced melanoma in 2023. Phase 3 trials test for safety and efficacy in larger groups of patients. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/modernas-experimental-cancer-vaccine-treats-but-doesnt-prevent-melanoma-a-biochemist-explains-how-it-works-197003">Moderna's experimental cancer vaccine treats but doesn't prevent melanoma – a biochemist explains how it works</a>
</strong>
</em>
</p>
<hr>
<p>BioNTech has several mRNA cancer candidates in the works, including for advanced melanoma, ovarian cancer and non-small cell lung cancer. It will release results from its own phase 2 melanoma trial (of 131 patients) using immunotherapy and an mRNA vaccine combination later this year. Its primary <a href="https://www.clinicaltrialsarena.com/features/mrna-vaccine-trials-to-watch/">aim</a> is to measure cancer progression and survival over 24 months in previously untreated patients. </p>
<p>A third company called CureVac is also developing mRNA vaccines <a href="https://pharmaceutical-journal.com/article/feature/how-close-are-we-to-developing-an-mrna-cancer-vaccine">targeting a range of cancers</a> including ovarian, colorectal, head and neck, lung and pancreatic. </p>
<p>CureVac has a deal with Tesla, the electric car manufacturer, to develop small, <a href="https://www.reuters.com/article/healthcoronavirus-tesla/update-2-tesla-to-make-molecule-printers-for-covid-19-vaccine-developer-curevac-idUSL4N2E926F">portable mRNA bioprinters</a> to automate the process of producing patient mRNA. These can be shipped to <a href="https://www.reuters.com/article/us-health-coronavirus-tesla-idUSKBN243168">remote locations</a> where they are able to churn out vaccine candidates based on the DNA template (recipe) fed into the machine.</p>
<p>A lot of these <a href="https://www.curevac.com/en/pipeline/">vaccines</a>, including those targeting cancer, are in pre-clinical to phase 1 stages of development, to test the effects and side effects in the laboratory, animal models or small groups of patients. </p>
<h2>When will they become available?</h2>
<p>Overseas, Moderna and Merck’s mRNA cancer vaccine was fast-tracked for review by the US FDA in February 2023. </p>
<p>Australia’s Therapeutic Goods Administration has not approved the use of mRNAs for use either alone or with other cancer treatments yet. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1628997661297635330"}"></div></p>
<p>In January 2023, the United Kingdom’s National Health Service <a href="https://www.theguardian.com/science/2023/jan/22/the-other-big-c-how-the-science-behind-covid-vaccines-might-help-to-fight-cancer">partnered</a> with BioNTech to fast-track the development of mRNA cancer vaccines over the next seven years. Eligible UK cancer patients will get early access to clinical trials from late 2023 onwards. By <a href="https://www.nature.com/articles/s41587-023-01693-z">2030</a>, these mRNA vaccines will be made clinically available to around 10,000 cancer patients.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/cancer-vaccine-trials-could-start-in-the-autumn-uk-signs-deal-with-biontech-197363">Cancer vaccine trials could start in the autumn – UK signs deal with BioNTech</a>
</strong>
</em>
</p>
<hr>
<p>In Australia, BioNTech is <a href="https://www.premier.vic.gov.au/biontech-coup-more-mrna-manufacturing-research-melbourne">establishing</a> its Asia-Pacific mRNA clinical research and development centre in Melbourne, in partnership with the Victorian government. This would <a href="https://www.biospace.com/article/releases/biontech-establishes-asia-pacific-clinical-scale-mrna-manufacturing-and-regional-research-centre/">develop</a> mRNA vaccines for research and clinical trials, including personalised cancer treatments.</p>
<p>Meanwhile, Moderna <a href="https://www.industry.gov.au/news/mrna-vaccine-manufacturing-facility-commences-construction-melbourne">will develop</a> Australia’s first large-scale mRNA vaccine facility at Monash University by 2024, in partnership with the state and federal government. This will give Australians <a href="https://www.globalaustralia.gov.au/news-and-resources/news-items/moderna-build-mrna-vaccine-manufacturing-facility-australia#:%7E:text=US%20biotech%20company%20Moderna%20has,doses%20each%20year%20in%20Australia.">priority access</a> to mRNA vaccines made locally.</p>
<h2>What else could the technology be used for?</h2>
<p>Aside from cancer, there is <a href="https://www.technologyreview.com/2023/01/05/1066274/whats-next-mrna-vaccines/">huge potential</a> to use mRNA technologies across many gene therapies.</p>
<p>There are <a href="https://pharmanewsintel.com/features/from-covid-to-cancer-understanding-the-applications-of-mrna-vaccines">studies underway</a> testing mRNA vaccines for various diseases such as evolving COVID strains, <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-initiates-phase-3-study-mrna-based-influenza-vaccine">seasonal influenza</a>, <a href="https://www.curevac.com/en/pipeline/">malaria</a>, <a href="https://www.nih.gov/news-events/news-releases/nih-launches-clinical-trial-three-mrna-hiv-vaccines">HIV</a>, <a href="https://www.businesswire.com/news/home/20221208005977/en/">cystic fibrosis</a> and even allergies, giving new hope for many previously incurable diseases.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/3-mrna-vaccines-researchers-are-working-on-that-arent-covid-157858">3 mRNA vaccines researchers are working on (that aren't COVID)</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/197988/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sathana Dushyanthen does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Cancer vaccines are an emerging personalised treatment for cancer. Using the same mRNA technology as COVID vaccines, they stimulate the immune system to destroy cancer cells.Sathana Dushyanthen, Academic Specialist & Lecturer in Cancer Sciences & Digital Health| Superstar of STEM| Science Communicator, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1982332023-02-26T19:06:02Z2023-02-26T19:06:02ZIs there a vaccine for RSV or respiratory syncytial virus? After almost 60 years, several come at once<figure><img src="https://images.theconversation.com/files/510804/original/file-20230217-22-p39gna.jpg?ixlib=rb-1.1.0&rect=1%2C4%2C997%2C556&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-asian-little-baby-boy-treated-1589743531">Shutterstock</a></span></figcaption></figure><p>You might not have heard of respiratory syncytial virus, or RSV. But it caused more than <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00478-0/fulltext">100,000 global deaths</a> in 2019, making it a leading cause of death in children under one year old.</p>
<p>In Australia, child deaths are thankfully <a href="https://pubmed.ncbi.nlm.nih.gov/34845151/">rare</a>. But infection sends thousands to hospital each year, particularly <a href="https://www.mja.com.au/journal/2019/210/10/respiratory-syncytial-virus-associated-hospitalisations-australia-2006-2015">babies and young children</a>.</p>
<p>So for kids, this virus is a very big deal. And despite almost 60 years of research, there are no licensed vaccines to prevent it.</p>
<p>That may change soon. We’ve recently had results of late-stage clinical trials of RSV vaccines from <a href="https://www.statnews.com/2023/01/17/moderna-says-rsv-vaccine-worked-setting-stage-for-competition-with-gsk-and-pfizer/">Pfizer, Moderna and GSK</a>. These vaccines are being assessed (or will be shortly) for regulatory approval in the United States.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1627678804960497664"}"></div></p>
<p>However, these trials were conducted in adults and pregnant women, not children. So we still have a way to go before RSV vaccines are tested in children, shown to be safe and effective, are approved for use, then become widely available.</p>
<p>Here’s why it’s taken so long to develop a RSV vaccine and what we can expect next.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rsv-experts-explain-why-rates-of-this-virus-are-surging-this-year-194403">RSV: experts explain why rates of this virus are surging this year</a>
</strong>
</em>
</p>
<hr>
<h2>What is RSV?</h2>
<p>RSV is a contagious virus causing respiratory infections in both adults and children.</p>
<p>The virus is transmitted from person to person by droplets when someone coughs or sneezes, or by touching their nose or eyes after touching contaminated surfaces.</p>
<p>Infections usually surge in winter, causing symptoms such as a runny nose, sneezing, sore throat, fever, headache and cough. Adults and children can be hospitalised with RSV and its complications, which include pneumonia and <a href="https://www.rch.org.au/kidsinfo/fact_sheets/Bronchiolitis/">bronchiolitis</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rsv-faq-what-is-rsv-who-is-at-risk-when-should-i-seek-emergency-care-for-my-child-195292">RSV FAQ: What is RSV? Who is at risk? When should I seek emergency care for my child?</a>
</strong>
</em>
</p>
<hr>
<h2>We’ve had a few setbacks</h2>
<p>The <a href="https://journals.asm.org/doi/10.1128/CVI.00609-15">first RSV vaccine</a> was given to infants and children in the mid-1960s. </p>
<p>Although this inactivated vaccine (composed of dead RSV particles) seemed to be well tolerated, it later caused a rare side effect called vaccine-enhanced disease. This is where the vaccine caused more serious RSV symptoms when infants and toddlers caught the virus, instead of protecting them.</p>
<p>This was almost 60 years ago, and the science of vaccine development has come a long way. Even though scientists later found new vaccine strategies, this disaster has unfortunately slowed down RSV vaccine research and development.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/randomised-control-trials-what-makes-them-the-gold-standard-in-medical-research-78913">Randomised control trials: what makes them the gold standard in medical research?</a>
</strong>
</em>
</p>
<hr>
<h2>Newer technologies, fresh hope</h2>
<p>Advances in what we know about the virus, and newer vaccine technologies, mean researchers are now more optimistic about the prospect of a RSV vaccine.</p>
<p>Ten years ago, <a href="https://www.science.org/doi/10.1126/science.1234914">scientists identified</a> the structure of the RSV viral protein it uses to attach and enter human host cells. This allowed scientists to change strategies and develop protein-based RSV vaccines.</p>
<p>Protein-based vaccines consist of injecting a purified protein from the target virus that stimulates the immune cells. This technology is used in many existing vaccines, such as those for hepatitis B and pertussis (whooping cough).</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1605357061583147009"}"></div></p>
<p>But it’s not been plain sailing for protein-based vaccines either.</p>
<p>In 2019, Novavax <a href="https://ir.novavax.com/2019-02-28-Novavax-Announces-Topline-Results-from-Phase-3-PrepareTM-Trial-of-ResVax-TM-for-Prevention-of-RSV-Disease-in-Infants-via-Maternal-Immunization">announced</a> its prototype protein-based RSV vaccine (ResVax) failed to prevent “medically significant” RSV in babies born to mothers who had been given the vaccine as part of a late-stage clinical trial.</p>
<p>Although the vaccine was shown to be safe, and protected babies from severe RSV, including hospitalisations, the vaccine has not yet made it to market, and further clinical trials <a href="https://www.precisionvaccinations.com/vaccines/resvax-rsv-vaccine">are ongoing</a>.</p>
<p>In recent years, we’ve seen another major technology development – mRNA vaccines. These have proved effective and robust during the COVID pandemic. </p>
<p>These mRNA vaccines involve injecting the information required for the human host cells to produce the viral protein, to later stimulate immune cells.</p>
<p>The front-runner RSV candidate vaccines – from GSK, Pfizer and Moderna – are either protein-based or use mRNA technology.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-fascinating-history-of-clinical-trials-139666">The fascinating history of clinical trials</a>
</strong>
</em>
</p>
<hr>
<h2>The GSK vaccines</h2>
<p>GSK is going with protein-based technology for two of its candidate RSV vaccines.</p>
<p>One (known as RSVPreF3 OA), has had good results in late-stage clinical trials in adults 60 years or older, with data published <a href="https://www.nejm.org/doi/10.1056/NEJMoa2209604">in recent weeks</a>. The US Food and Drug Administration (FDA) <a href="https://www.gsk.com/en-gb/media/press-releases/gsk-s-rsv-oa-vaccine-candidate-granted-priority-review-by-us-fda/">is reviewing</a> the vaccine, with results expected in May.</p>
<p>Another of GSK’s candidate RSV vaccines (GSK3888550A, RSVPreF3) is taking a different approach. The idea is to vaccinate pregnant women to confer immunity to the unborn baby.</p>
<p>Results of late-stage trials in healthy pregnant women aged 18-49 years are <a href="https://www.gsk.com/en-gb/media/press-releases/gsk-starts-phase-3-study-of-rsv-maternal-candidate-vaccine/">set to report in 2024</a>. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200160/">Earlier studies</a> in non-pregnant women showed the vaccine was well tolerated and activated a good immune response.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Pregnant Muslim woman clutching belly looking at phone in hand in front of window" src="https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Some candidate RSV vaccines are given to pregnant women to protect their babies.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-pregnant-arab-woman-hijab-using-1407599552">Shutterstock</a></span>
</figcaption>
</figure>
<h2>The Pfizer vaccine</h2>
<p>Pfizer has also gone with a protein-based RSV vaccine (RSVpreF). But this time it’s a bivalent vaccine. It contains proteins to stimulate immune protection against two types of RSV – RSV A and B. Again, the idea again is to vaccinate pregnant women to immunise their babies in the womb.</p>
<p>In November 2022, Pfizer <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-data-phase-3-global">announced</a> interim results of its <a href="https://clinicaltrials.gov/ct2/show/NCT04424316?term=RSVpreF+pfizer&phase=2&draw=2&rank=2">late-stage clinical trial</a> showing 81.8% efficacy in protecting against severe disease in babies (one to 90 days old) of vaccinated pregnant women. Over time, that immunity decreased.</p>
<p>Final clinical trial results are expected <a href="https://www.pfizer.com/news/press-release/press-release-detail/us-fda-accepts-biologics-license-application-pfizers">any day now</a>, and the vaccine is being submitted to the FDA for priority review, with a result expected in August.</p>
<h2>The Moderna vaccine</h2>
<p>Moderna is using mRNA technology for its candidate RSV vaccine (called mRNA-1345). It uses similar technology to its COVID mRNA vaccines.</p>
<p>It has been tested in <a href="https://clinicaltrials.gov/ct2/results?term=mRNA-1345&age_v=&gndr=&type=&rslt=&Search=Apply">late-stage clinical trials</a> in people over the age of 60. The <a href="https://investors.modernatx.com/news/news-details/2023/Moderna-Announces-mRNA-1345-an-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Has-Met-Primary-Efficacy-Endpoints-in-Phase-3-Trial-in-Older-Adults/default.aspx">company announced</a> earlier this year that the vaccine was mostly well tolerated and had an efficacy of 83.7%.</p>
<p>The company is set to make a <a href="https://investors.modernatx.com/news/news-details/2023/Moderna-Granted-FDA-Breakthrough-Therapy-Designation-for-mRNA-1345-An-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Candidate/default.aspx">full submission</a> to the FDA in the first half of 2023.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/3-mrna-vaccines-researchers-are-working-on-that-arent-covid-157858">3 mRNA vaccines researchers are working on (that aren't COVID)</a>
</strong>
</em>
</p>
<hr>
<h2>Several hurdles ahead</h2>
<p>Another candidate vaccine, <a href="https://www.janssen.com/janssen-announces-respiratory-syncytial-virus-rsv-adult-vaccine-candidate-maintains-high-efficacy">from Janssen</a>, uses a different type of technology (adenovirus vector technology), and is not so far advanced through clinical trials as the others. But it has shown <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9417128/">promising preliminary results</a> <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2207566?query=recirc_curatedRelated_article">to date</a> in adults.</p>
<p>And that’s the sticking point with all the RSV vaccines mentioned. They’ve only been tested in adults. To have the greatest impact, the vaccines must also be evaluated in young children and infants. </p>
<p>The biggest question is what age should a baby be vaccinated against RSV once it loses the immunity from its mother?</p>
<p>While we wait for RSV vaccines, the best way of slowing the spread of this viral illness are measures we’ve become used to during COVID. If you or your children have RSV, make sure you wear a mask, wash your hands and maintain your distance from others.</p>
<hr>
<p><em>We would like to thank Masters (Doctor of Medicine) student Chloe Scott from Griffith University for her critical review and assistance with this article.</em></p><img src="https://counter.theconversation.com/content/198233/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lara Herrero receives funding from NHMRC
</span></em></p><p class="fine-print"><em><span>Wesley Freppel does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Here’s why it’s taken so long to develop a vaccine for respiratory syncytial virus and what we can expect next.Lara Herrero, Research Leader in Virology and Infectious Disease, Griffith UniversityWesley Freppel, Research Fellow, Institute for Glycomics, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1977462023-02-13T20:36:07Z2023-02-13T20:36:07ZAdvantages and challenges of anti-Covid nasal vaccination: the promises of a French approach<figure><img src="https://images.theconversation.com/files/505146/original/file-20230118-12-aox0t5.png?ixlib=rb-1.1.0&rect=0%2C149%2C2000%2C1089&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A team from the University of Tours and INRAE is working on the development of an innovative nasal vaccine against Covid, in spray form.</span> <span class="attribution"><span class="source">LoValTech</span>, <span class="license">Fourni par l'auteur</span></span></figcaption></figure><p>Contrary to the widely shared popular belief, the primary purpose of current vaccines against Covid-19 is solely to protect against serious forms of the disease in order to prevent the risk of hospitalisations and death… and not to block transmission between individuals. To do this, it would be necessary to aim for a so-called sterilising vaccination: only then could the circle of contamination be interrupted, allowing to stop the pandemic.</p>
<p>How to reach this level of efficacy? In general, vaccination allows the induction of an immune response based on two types of cells: T lymphocytes, capable of destroying infected cells, and B lymphocytes which produce antibodies capable of neutralising the virus (SARS-CoV-2 in the case of Covid) to prevent it from multiplicating and infecting new healthy cells.</p>
<p>Current vaccines (including mRNA) are administered intramuscularly and are so called “systemic”: they allow the activation at the level of the whole body of a pool of immune cells, circulating by the blood, which can further reach the infected organs.</p>
<p>Effective as it is, this systemic immunity does not allow the mobilisation of a high level of B and T lymphocytes in the nasal cavity and the lungs – to promote a rapid and effective protection against the virus – blocking it as soon as it arrives.</p>
<p>Conversely, an intranasal vaccination induces not only a systemic but also a local immune response – directly, therefore, at the gate of the entry of SARS-CoV-2. The local activation of the immune cells of the nasal mucosa would thus make it possible to overcome the race against time between the virus (which multiplies in our respiratory system) and our systemic immune system (which need to be mobilised to the infected site). Concretely this mucosal vaccination would quickly stop the virus and block its possibilities of dissemination and replication in our organism and thus avoid transmission and contamination.</p>
<h2>The specifics of nasal vaccination</h2>
<p>First observation, as we said, only the nasal vaccination can act directly at the level of entry of the virus. But we should also mention that the immune cells it activates there (resident T and B lymphocytes in the nose, mouth and upper respiratory tract) differ from those activated by the conventional (i.e., systemic) intramuscular vaccination. Moreover: nasal vaccination induces B lymphocytes that produce particular antibodies, IgA (Type A immunoglobulins), which are only very weakly induced by the intramuscular route – which mainly induces B cells producing IgG (Type G immunoglobulins).</p>
<p>Worst noting: IgAs have a greater capacity than IgGs to “capture” viruses in order to neutralise them. Another advantage of IgAs: they are more “versatile” than IgGs and thus can retain a significant level of effectiveness despite possible variations in the virus. For all these reasons, “mucosal” vaccination would prevent even moderate forms of the disease and block inter-individual transmission, to achieve sterilising immunity.</p>
<p>The <a href="https://www.flumistquadrivalent.com/">FluMist vaccine</a> is the only example of intranasal vaccine available in human health that has received marketing authorisation (AMM). This flu vaccine is based on an attenuated form of the causative virus (influenza), approved in the United States and Europe, and has <a href="https://www.nejm.org/doi/full/10.1056/nejmoa065368">an efficacy that surpasses that of the intramuscular vaccine in young children</a>. However, its effectiveness is lower in adults owing to their already acquired mucosal immunity, due to previously contracted infections. Indeed, consisting of an attenuated version of the virus, the vaccine is quickly blocked by the local immunity in place reacting against the original virus: which leaves it less likely to act efficiently.</p>
<h2>New nasal vaccine approach</h2>
<p>Our research team (BioMAP laboratory, Joint University-INRAE ISP 1282 research unit), led by Professor Isabelle Dimier-Poisson, has recognised experience in immunology and mucosal vaccination. Based on our expertise, we have worked on an innovative anti-Covid mucosal vaccine strategy in order to deal with its multiple specificities. Our vaccine candidate is based on three innovations:</p>
<ul>
<li><p>The antigen: target of the virus, it represents the heart of the vaccine. It is an original fusion protein, designed in our laboratory, composed of the now-famous Spike (S) protein associated with another protein of the virus, the nucleoprotein (N). This fusion strategy allows our vaccine to maintain its efficacy against different variants since it targets some conserved parts of the virus, whatever the <a href="https://theconversation.com/how-new-Covid-19-variants-emerge-natural-selection-and-the-evolution-of-sars-cov-2-176030">variations of the S protein</a>.</p></li>
<li><p>To optimise the activation of the mucosal immune response, our antigen is wrapped in “nano-carriers”. These nano-carriers are solely composed of sugar polymeric molecules, able to confer original properties of adhesion to the mucous membrane allowing an optimal administration of our protein. In this manner there is no need for an adjuvant (likely to create inflammation), thus reducing the risk of side effects.</p></li>
<li><p>Finally, the last key element, a dedicated delivery system, or spray, capable of effectively depositing our vaccine in the nasal cavity, precisely at the level of the areas containing the mucosal immune cells.</p></li>
</ul>
<h2>Nasal anti-Covid vaccination: where are we?</h2>
<p>Other teams are following this type of approach to develop anti-Covid vaccine delivered by the mucosal route. However, there are still very few vaccine candidates available in humans. We can mention two recent examples (September 2022), in China and India – bearing in mind that they do not use the intranasal route in the strict sense. A first vaccine, currently <a href="https://www.reuters.com/world/china/china-rolls-out-first-inhalable-Covid-vaccine-2022-10-28/">being tested in China</a>, is administered by inhalation. CanSino Biologics’ vaccine has been approved by Chinese health authorities as a booster dose to protect against symptoms of Covid-19. It is based, like its intradermal counterpart, on a recombinant adenovirus expressing the S protein of SARS-CoV-2 and is delivered using a nebuliser through the mouth. It therefore requires a specific medical device and, due to its viral nature, even attenuated, presents a risk of side effects such as pulmonary inflammation. The second has been approved by the Indian health authorities: iNCOVACC, developed by <a href="https://www.bharatbiotech.com/intranasal-vaccine.html">Bharat Biotech</a>, for primary vaccination in two doses administered through the nose.</p>
<p>This nasal vaccine similarly uses a modified and attenuated adenovirus to deliver the Spike protein of SARS-CoV-2. This vaccine, created by <a href="https://infectiousdiseases.wustl.edu/michael-s-diamond-md-phd-creates-worlds-first-nasal-Covid-19-vaccine-approved-in-india/">Michael S. Diamond, David T. Curiel (University of Washington)</a>, was the subject of a recent <a href="https://www.biorxiv.org/content/10.1101/2021.01.26.428251v1">publication presenting preclinical trials in chimpanzees</a>, and showing promising results. However, this result is not representative of a “true” nasal vaccination since it uses a dual route of vaccination: intranasal and intrabronchial. In this manner the vaccine is administered to the lungs, with a potential risk of inflammation. This preclinical result should therefore be considered with caution. It’s also worth noting that neither China nor India has yet released the results of human clinical studies supporting their decision to approve these vaccines. Regardless of the considered candidate, the ability to administer the vaccine formulation effectively via the nasal route is a challenge.</p>
<p>AstraZeneca has just announced in October the <a href="https://www.ox.ac.uk/news/2022-10-11-intranasal-Covid-19-vaccine-candidate-s-clinical-data-highlights-need-further">disappointing results of its first clinical trials of a nasal vaccine</a>. This nasally administered version of its injectable vaccine (developed with researchers at the University of Oxford) showed only weak antibody responses in the nasal mucosa. The explanation would be that a large part of the vaccine, which uses a deactivated virus, would not have reached its target and would have ended up largely in the digestive tract before it could activate the immune system of the mucous membranes. A key point, which is underlined by the team of this latest vaccine candidate, is the importance of the spray system. Vaccination by nasal administration clearly requires consideration to optimise the in situ product delivery.</p>
<h2>Final steps for our vaccine candidate</h2>
<p>Our vaccine candidate has given excellent results against multiple variants of SARS-CoV-2, with protection against the disease and significant limitation of its transmission, in gold standard preclinical models (mice and hamsters). Our objective is now to validate its efficacy during clinical trials in humans, scheduled for 2023. The challenge, to go from preclinical to human, is to obtain an effective immune response despite a different delivery of the vaccine: indeed, in the mouse and hamster models, the volume of vaccine used and its delivery using micropipette deposition in the nose induce immunisation not restricted to the nasal cavity but also reaching the upper part of the lungs.</p>
<p>However, in humans, we want to stay at the level of the nasal cavity in order to limit the risks of an uncontrolled immune reaction that can lead to an excessively strong inflammatory reaction in the lung (<a href="https://theconversation.com/inflammation-the-key-factor-that-explains-vulnerability-to-severe-Covid-144768">“cytokine storms”</a>): the objective is to optimise the stimulation of the nasal mucosal system only. To do this, we want our vaccine to be completely deposited in the critical areas of the nose: where the virus nests to infect and multiply, and where the immune cells that must respond to the vaccine are located (at the level of the NALT, or Nasal Associated Lymphoid Tissues, where IgA-producing B lymphocytes and T lymphocytes are concentrated).</p>
<h2>Developing a spray system suitable for nasal vaccination</h2>
<p>Small nuance: a vaccine spray is different from a classical therapeutic spray used for multiple and repeated use. It must deliver a single, very precise dose targeting the mucosal immune system. From the start of our project, we began to work on those absolute prerequisite and set up research and development collaborations with two companies specialised in intranasal delivery systems: <a href="https://www.aptar.com/products/pharmaceutical/nasal-vaccines/">Aptar pharma</a> and <a href="https://medspray.com/cases/nasal-atomiser-adapter/">Medspray</a>. The potential effectiveness of the spray systems is assessed by two methods:</p>
<ul>
<li><p>In vitro, using an artificial model (nasal cast) which reproduces the human nasal cavity and makes it possible to assess, after adding a fluorescent dye, how our vaccine formulation is deposited in the different compartments. This model allows us to correct the spray to optimally target key immune system areas of the nasal mucosa.</p></li>
<li><p>In vivo, we carry out comparative efficacy tests of the various spray systems in rabbits (among the gold standard animal model) to assess their ability to induce an optimal vaccine response in the nasal mucosa (in the context of regulatory toxicology tests).</p></li>
</ul>
<p>Our goal is to select the optimal intranasal delivery system for future clinical trials, in terms of biological efficacy (maximal vaccination efficacy despite a delivery restricted to the nasal cavity). In addition, with the idea of designing a spray accessible to low-income countries, we are considering economic constraints to ensure that it can be mass-produced at reduced cost.</p>
<hr>
<p><em>To support our vaccine candidate, our team created the start-up <a href="https://lovaltechnology.com/en/home/">LoValTech</a> in 2022 in order to take over our academic research and follow its industrial development until its commercialisation.</em></p><img src="https://counter.theconversation.com/content/197746/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mathieu Epardaud is one of the co-founders of LoValTech, for which he works as a scientific consultant (unpaid).</span></em></p>Vaccination is often combined with an injection. It can also take the form of a nasal spray: an approach that is still rare, but which could be effective against Covid. Here’s why.Mathieu Epardaud, Research Associate, InraeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1958072023-02-07T13:33:23Z2023-02-07T13:33:23ZHow do you make a universal flu vaccine? A microbiologist explains the challenges, and how mRNA could offer a promising solution<figure><img src="https://images.theconversation.com/files/508472/original/file-20230206-31-mtkppf.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Broad protection from a universal flu vaccine could replace seasonal flu shots.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/influenza-vaccine-vials-pattern-background-royalty-free-image/1365216790">Flavio Coelho/Moment via Getty Images</a></span></figcaption></figure><p>To everything there is a season, and for the flu, it’s wintertime. Flu cases <a href="https://www.cdc.gov/flu/about/season/flu-season.htm">peak between December and February</a>, and the flu vaccine is your best defense. Getting the vaccine means you <a href="https://www.cdc.gov/flu/prevent/keyfacts.htm">will be less sick</a> even if you get a breakthrough infection. </p>
<p>However, your immune system is in a constant race against the flu virus. Like the virus that causes COVID-19, influenza rapidly changes and mutates into new variants, so manufacturers have to update the flu shot to <a href="https://www.doi.org/10.1126/science.aaq0105">try to keep pace</a>. After identifying a new flu variant, it takes manufacturers about six months to update the vaccine – and in the meantime the virus can mutate again. This phenomenon is called <a href="https://doi.org/10.1146/annurev-virology-010320-044746">antigenic drift</a>, and can reduce the effectiveness of the flu vaccine for that season. </p>
<p>An ongoing threat is that a major change in the flu virus, or <a href="https://www.cdc.gov/flu/about/viruses/change.htm">antigenic shift</a>, could cause the next flu pandemic. This happens when a flu virus from animals, such as birds or swine, gains the ability to transmit between humans. Most people will have no immunity against this new animal-origin virus, so it could quickly spread into a pandemic. If that happens, the annual flu shot will not be effective and can’t be updated fast enough to stop a global spread.</p>
<p><a href="https://scholar.google.com/citations?user=eNprtJEAAAAJ&hl=en">I am a researcher</a> developing new vaccines to prevent future pandemics. Nearly 20 years ago, my lab and several others developed a vision of building a <a href="https://doi.org/10.1101%2Fcshperspect.a028845">universal influenza vaccine</a> that could give us the leading edge in the race against influenza and prevent the next flu pandemic by effectively combating any eventual flu strain. One potential way to do this is with messenger RNA, or mRNA.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/0k1Qg9OlfRs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">A primary challenge in developing vaccines against influenza is how rapidly the virus mutates.</span></figcaption>
</figure>
<h2>What is a universal influenza vaccine?</h2>
<p>A universal influenza vaccine is one that does not need to be updated each year because it is designed to protect against all or most influenza variants. Scientists are exploring several ways to develop universal influenza vaccines. Most fall into <a href="https://doi.org/10.1093/infdis/jiy103">one of two buckets</a>. </p>
<p>The first includes vaccines that focus on conserved, or unchanging, parts of the virus. This strategy directs the immune system against parts of the virus, or antigens, that are shared among all variants and can’t mutate without weakening or killing the virus.</p>
<p>The second includes mosaic vaccines. These are like a cocktail of protein pieces taken from different variants. The blend is made up of versions of the protein hemagglutinin – essential to the influenza virus’s ability to infect cells – that is found in all flu variants circulating in animals and people. The goal is to induce immunity against nearly all variants so there will be fewer gaps in the immune system’s defenses for the virus to slip through.</p>
<h2>Using mRNA for a universal flu vaccine</h2>
<p>The recent success of mRNA vaccines for COVID-19 shows promise for their use in achieving the vision of an effective universal influenza vaccine. </p>
<p>There are 20 known subtypes of influenza. Prior to the development of mRNA vaccines, it wasn’t feasible to make a single flu vaccine against all 20 subtypes due to the complexities and costs in manufacturing. Unlike traditional vaccines, constructing and producing mRNA vaccines is rapid and simple because manufacturers don’t have to produce and purify the protein directly. Instead, mRNA vaccines provide the genetic sequence of the protein and then use the body’s own cells to generate that protein <a href="https://doi.org/10.1073/pnas.2123477119">in its natural structure</a>. This makes it relatively easy to incorporate any antigen or many antigens.</p>
<p>Recently, a team of researchers <a href="https://doi.org/10.1126/science.abm0271">designed a mosaic mRNA vaccine</a> with sequences from multiple versions of the hemagglutinin protein, each representing one of the 20 influenza subtypes. This vaccine induced broad immunity against each variant in mice and ferrets.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/z0kfdZ8o_j4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">mRNA vaccines circumvent some of the manufacturing challenges traditional vaccines face.</span></figcaption>
</figure>
<p>Several research groups are also exploring the conserved antigen approach with mRNA vaccines. Animal studies have shown that it’s possible to design mRNA vaccines that can both focus immune responses against highly conserved, vulnerable parts of the virus and <a href="https://doi.org/10.1126/sciadv.adc9937">induce</a> <a href="https://doi.org/10.1016/j.ymthe.2020.04.018">broad immunity</a> against a wide range of different influenza subtypes. These include <a href="https://doi.org/10.1073/pnas.2206333119">avian flu viruses</a> that share many genetic sequences with human influenza. </p>
<p>Another promising approach uses <a href="https://give.uwmedicine.org/stories/designing-a-pandemic-free-future/">computational modeling</a> to leverage both conserved and mosaic approaches. This strategy displays multiple hemagglutinins from different influenza subtypes <a href="https://doi.org/10.3389/fimmu.2019.00022">on a nanoparticle</a>. Nanoparticles are structures that give researchers more precise control over how the immune system sees the viral antigens, subsequently allowing them to induce stronger immune responses against multiple variants. Here, both conserved and variable regions of the virus are exposed to the immune system and can lead to <a href="https://doi.org/10.1038/s41586-021-03365-x">broad immunity</a>.</p>
<h2>Obstacles to a universal flu mRNA vaccine</h2>
<p>There are still several challenges before a universal influenza mRNA vaccine can be made available. </p>
<p>For one, it is not clear which conserved antigens provide the broadest protection, and some don’t naturally induce strong immune responses. So, mRNA vaccines may need improvements like additional components that help activate immune cells. One such addition could include <a href="https://doi.org/10.1073/pnas.2217533119">using mRNA to express nanoparticles</a> that stimulate stronger immune responses against the conserved antigens presented by the vaccine.</p>
<p>The mosaic approach is also limited by the <a href="https://doi.org/10.1056/NEJMoa2022483">maximum dose possible</a> for mRNA vaccines, because higher doses could cause increased adverse reactions to the vaccine. When that dose gets divided into 20 or more antigens, the dose of one or more of those antigens may drop below the threshold needed for protection.</p>
<p>Scientists are working on these challenges, including by developing <a href="https://doi.org/10.1126/science.abq6562">new mRNA technologies</a> that work with a much lower dose. If mRNA vaccines work for universal protection from influenza, the same strategies could also <a href="https://theconversation.com/how-mrna-and-dna-vaccines-could-soon-treat-cancers-hiv-autoimmune-disorders-and-genetic-diseases-170772">apply to other frequently mutating viruses</a>, such as the virus that causes COVID-19 and maybe even HIV.</p>
<p>In the meantime, mRNA vaccines may soon <a href="https://doi.org/10.1073/pnas.2217533119">usher in a new era</a> of more effective annual flu vaccines by providing a better match to each flu season’s new variants. <a href="https://www.clinicaltrialsarena.com/features/mrna-vaccine-trials-to-watch/">Two seasonal influenza mRNA vaccines</a> are currently in human clinical trials. If successful, they may offer more effective protection from the annual flu than our current flu vaccines. With mRNA vaccines, I believe that we are at the beginning of starting a new race against flu that we may finally win.</p><img src="https://counter.theconversation.com/content/195807/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Deborah Fuller is a co-founder of Orlance, Inc. a biotechnology company developing a needle-free delivery technology for DNA and RNA vaccine. She also serves as a consultant for HDT Bio, a biotechnology company developing nanoparticle-based formulations to deliver RNA vaccines and Abacus Inc., a therapeutic vaccine company developing B cell targeted therapies for chronic infectious diseases and cancer. She receives grant funding from the National Institutes of Health, the Washington Research Foundation and the Department of Defense.</span></em></p>Annual flu vaccines are in a constant race against a rapidly mutating virus that may one day cause the next pandemic. A one-time vaccine protecting against all variants could give humanity a leg up.Deborah Fuller, Professor of Microbiology, School of Medicine, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1970032023-01-17T13:33:25Z2023-01-17T13:33:25ZModerna’s experimental cancer vaccine treats but doesn’t prevent melanoma – a biochemist explains how it works<figure><img src="https://images.theconversation.com/files/503900/original/file-20230110-22-kni45q.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2120%2C1414&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Moderna is testing an mRNA vaccine in combination with pembrolizumab to treat melanoma.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/mrna-vaccine-vial-for-cancer-immunotherapy-on-blue-royalty-free-image/1311515350">Javier Zayas Photography/Moment via Getty Images</a></span></figcaption></figure><p><a href="https://www.washingtonpost.com/health/2022/12/13/experimental-cancer-vaccine-messenger-rna-melanoma/">Media</a> <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/moderna-merck-vaccine-combo-cut-melanoma-recurrence-by-44-study-2022-12-13/">outlets</a> have reported the encouraging findings of clinical trials for a new experimental vaccine developed by the biotech company <a href="https://investors.modernatx.com/news/news-details/2022/Moderna-and-Merck-Announce-mRNA-4157V940-an-Investigational-Personalized-mRNA-Cancer-Vaccine-in-Combination-with-KEYTRUDAR-pembrolizumab-Met-Primary-Efficacy-Endpoint-in-Phase-2b-KEYNOTE-942-Trial/default.aspx">Moderna</a> to treat an aggressive type of skin cancer called <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/melanoma">melanoma</a>. </p>
<p>Although this is potentially very good news, it occurred to me that the headlines may be unintentionally misleading. The vaccines most people are familiar with prevent disease, whereas this experimental new skin cancer vaccine treats only patients who are already sick. Why is it called a vaccine if it does not prevent cancer?</p>
<p>I am a <a href="https://scholar.google.com/citations?user=iAbB1kMAAAAJ&hl=en">biochemist</a> and <a href="https://medicine.buffalo.edu/faculty/profile.html?ubit=mrobrian">molecular biologist</a> studying the roles that microbes play in health and disease. I also teach cancer genetics to medical students and am interested in how the public understands science. While preventive and therapeutic vaccines are administered for different health care goals, they both train the immune system to recognize and fight off a specific disease agent that causes illness.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/503907/original/file-20230110-26-2w4dwp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of melanoma" src="https://images.theconversation.com/files/503907/original/file-20230110-26-2w4dwp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/503907/original/file-20230110-26-2w4dwp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/503907/original/file-20230110-26-2w4dwp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/503907/original/file-20230110-26-2w4dwp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/503907/original/file-20230110-26-2w4dwp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/503907/original/file-20230110-26-2w4dwp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/503907/original/file-20230110-26-2w4dwp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Melanoma is an aggressive form of skin cancer.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/melanoma-skin-cancer-royalty-free-image/1134489746">Callista Images/Image Source via Getty Images</a></span>
</figcaption>
</figure>
<h2>How do preventive vaccines work?</h2>
<p>Most vaccines are administered to healthy people before they get sick to prevent illnesses caused by viruses or bacteria. These include vaccines that prevent polio, measles, COVID-19 and many other diseases. Researchers have also developed vaccines to <a href="https://www.cancer.org/healthy/cancer-causes/infectious-agents/infections-that-can-lead-to-cancer/viruses.html">prevent some types of cancers</a> that are caused by such viruses as the human papillomaviruses and Epstein-Barr virus.</p>
<p>Your <a href="https://www.niaid.nih.gov/research/immune-system-overview">immune system</a> recognizes objects such as certain microbes and allergens that do not belong in your body and initiates a series of cellular events to attack and destroy them. Thus, a virus or bacterium that enters the body is recognized as something foreign and triggers an immune response to fight off the microbial invader. This results in a <a href="https://med.libretexts.org/Bookshelves/Anatomy_and_Physiology/Book%3A_Anatomy_and_Physiology_(Boundless)/20%3A_Immune_System/20.6%3A_Humoral_Immune_Response/20.6D%3A_Immunological_Memory">cellular memory</a> that will elicit an even faster immune response the next time the same microbe intrudes.</p>
<p>The problem is that sometimes the initial infection causes serious illness before the immune system can mount a response against it. While you may be better protected against a second infection, you have suffered the potentially damaging consequences of the first one.</p>
<p>This is where preventive vaccines come in. By introducing a harmless version or a portion of the microbe to the immune system, the body can learn to mount an effective response against it without causing the disease.</p>
<p>For example, the <a href="https://www.cdc.gov/vaccines/vpd/hpv/public/index.html">Gardasil-9 vaccine</a> protects against the human papillomavirus, or HPV, which causes cervical cancer. It contains protein components found in the virus that cannot cause disease but do elicit an immune response that protects against future HPV infection, thereby preventing cervical cancer. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/KOz-bNhEHhQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The HPV vaccine can prevent cervical cancer.</span></figcaption>
</figure>
<h2>How does the Moderna cancer vaccine work?</h2>
<p>Unlike cervical cancer, skin melanoma isn’t caused by a viral infection, according the <a href="https://doi.org/10.1002/jmv.27924">latest evidence</a>. Nor does Moderna’s experimental vaccine prevent cancer as Gardasil-9 does.</p>
<p>The Moderna vaccine trains the immune system to fight off an invader in the same way preventive vaccines most people are familiar with do. However, in this case the invader is a tumor, a rogue version of normal cells that harbors abnormal proteins that the immune system can recognize as foreign and attack.</p>
<p>What are these abnormal proteins and where do they come from?</p>
<p>All cells are made up of proteins and other biological molecules such as carbohydrates, lipids and nucleic acids. Cancer is caused by mutations in regions of genetic material, or DNA, that encode instructions on what proteins to make. Mutated genes result in abnormal proteins called <a href="https://www.ucir.org/therapies/neoantigen-based-therapy">neoantigens</a> that the body recognizes as foreign. That can trigger an immune response to fight off a nascent tumor. However, sometimes the immune response fails to subdue the cancer cells, either because the immune system is unable to mount a strong enough response or the cancer cells have found a way to circumvent the immune system’s defenses.</p>
<p>Moderna’s experimental melanoma vaccine contains genetic information that encodes for portions of the neoantigens in the tumor. This genetic information is in the form of <a href="https://theconversation.com/what-is-mrna-the-messenger-molecule-thats-been-in-every-living-cell-for-billions-of-years-is-the-key-ingredient-in-some-covid-19-vaccines-158511">mRNA</a>, which is the same form used in the Moderna and <a href="https://www.pfizer.com/products/product-detail/pfizer-biontech-covid-19-vaccine">Pfizer-BioNtech</a> COVID-19 vaccines. Importantly, the vaccine cannot cause cancer, because it encodes for only small, nonfunctional parts of the protein. When the genetic information is translated into those protein pieces in the body, they trigger the immune system to mount an attack against the tumor. Ideally, this immune response will cause the tumor to shrink and disappear. </p>
<p>Notably, the Moderna melanoma vaccine is tailor-made for each patient. Each tumor is unique, and so the vaccine needs to be unique as well. To customize vaccines, researchers first biopsy the patient’s tumor to determine what neoantigens are present. The vaccine manufacturer then designs specific mRNA molecules that encode those neoantigens. When this custom mRNA vaccine is administered, the body translates the genetic material into proteins specific to the patient’s tumor, resulting in an immune response against the tumor.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/vponeaNiewE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Identifying the neoantigens of a tumor can help researchers personalize cancer vaccines.</span></figcaption>
</figure>
<h2>Combining vaccination with immunotherapy</h2>
<p>Vaccines are a form of <a href="https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy.html">immunotherapy</a>, because they treat diseases by harnessing the immune system. However, other immunotherapy cancer drugs are not vaccines because, while they also stimulate the immune system, they do not target specific neoantigens.</p>
<p>In fact, the Moderna vaccine is co-administered with the immunotherapy drug <a href="https://www.cancer.gov/about-cancer/treatment/drugs/pembrolizumab">pembrolizumab</a>, which is marketed as Keytruda. Why are two drugs needed?</p>
<p>Certain immune cells called <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/t-cell">T-cells</a> have <a href="https://doi.org/10.21037/aob-21-3">molecular accelerator and brake components</a> that serve as checkpoints to ensure they are revved up only in the presence of a foreign invader such as a tumor. However, sometimes tumor cells find a way to keep the T-cell brakes on and suppress the immune response. In these cases, the Moderna vaccine correctly identifies the tumor, but T-cells cannot respond to it. </p>
<p>Pembrolizumab, however, can bind directly to a brake component on the T-cell, inactivating the brake system and allowing the immune cells to attack the tumor.</p>
<p>Although pembrolizumab is <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2021/adjuvant-pembrolizumab-early-stage-melanoma">currently used by itself</a> to treat melanoma, recent clinical trials show additional benefits when combined with the Moderna vaccine. In those studies, the company reported that administering the mRNA vaccine with pembrolizumab <a href="https://investors.modernatx.com/news/news-details/2023/Moderna-and-Merck-Announce-mRNA-4157-V940-an-Investigational-Individualized-Neoantigen-Therapy-in-Combination-with-KEYTRUDAR-Pembrolizumab-Demonstrated-Superior-Recurrence-Free-Survival-in-Patients-with-High-Risk-Stage-IIIIV-Melanoma-Following-Comple/default.aspx">reduced the risk of recurrence or death by 44%</a> compared to pembrolizumab alone in melanoma patients who were at high risk of recurrence. </p>
<h2>Not a preventive cancer vaccine</h2>
<p>So why can’t the Moderna vaccine be administered to healthy people to prevent melanoma before it arises? </p>
<p>Cancers are highly variable from person to person. Each melanoma harbors a different neoantigen profile that cannot be predicted in advance. Therefore, a vaccine cannot be developed in advance of the illness.</p>
<p>The experimental mRNA melanoma vaccine, currently still in early-phase clinical trials, is an example of the new frontier of personalized medicine. By understanding the molecular basis of diseases, researchers can explore how their underlying causes vary among people, and offer personalized therapeutic options against those diseases.</p>
<p><em>This article was updated to note new clinical trial findings presented on April 16, 2023.</em></p><img src="https://counter.theconversation.com/content/197003/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark R. O'Brian receives funding from the National Institutes of Health.</span></em></p>Preventive and therapeutic vaccines both train the immune system to fight disease, but they are used in different ways.Mark R. O'Brian, Professor and Chair of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at BuffaloLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1976022023-01-16T23:55:32Z2023-01-16T23:55:32ZFAQ on COVID-19 subvariant XBB.1.5: What is it? Where is it prevalent? How does it differ from Omicron? Does it cause serious illness? How can I protect myself? Why is it nicknamed ‘Kraken’?<figure><img src="https://images.theconversation.com/files/504746/original/file-20230116-14-fkca7k.jpg?ixlib=rb-1.1.0&rect=281%2C32%2C6216%2C3757&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">XBB.1.5 is rapidly spreading across the globe and will likely become the next dominant COVID-19 subvariant.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/faq-on-covid-19-subvariant-xbb-1-5--what-is-it-where-is-it-prevalent-how-does-it-differ-from-omicron-does-it-cause-serious-illness-how-can-i-protect-myself-why-is-it-nicknamed--kraken-" width="100%" height="400"></iframe>
<p>Despite intensive public health efforts to grind the COVID-19 pandemic to a halt, the recent emergence of the highly transmissible, extensively drug-resistant and profoundly immune system-evading XBB.1.5 SARS-CoV-2 subvariant is putting the global community on edge.</p>
<h2>What is XBB.1.5?</h2>
<p>In the naming convention for SARS-CoV-2 lineages, the <a href="https://virological.org/t/pango-lineage-nomenclature-provisional-rules-for-naming-recombinant-lineages/657">prefix “X” denotes a pedigree that arose through genetic recombination</a> between two or more subvariants. </p>
<p>The XBB lineage emerged following natural <a href="https://www.who.int/news/item/27-10-2022-tag-ve-statement-on-omicron-sublineages-bq.1-and-xbb">co-infection of a human host with two Omicron subvariants, namely BA.2.10.1 and BA.2.75</a>. It was <a href="https://doi.org/10.1007/s12291-022-01109-w">first identified by public health authorities in India during summer 2022</a>. XBB.1.5 is a direct descendent, or more accurately, the “fifth grandchild” of the original XBB subvariant.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/504369/original/file-20230113-24-li24wl.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of the genetic lineage of a COVID-19 subvariant" src="https://images.theconversation.com/files/504369/original/file-20230113-24-li24wl.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/504369/original/file-20230113-24-li24wl.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=355&fit=crop&dpr=1 600w, https://images.theconversation.com/files/504369/original/file-20230113-24-li24wl.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=355&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/504369/original/file-20230113-24-li24wl.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=355&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/504369/original/file-20230113-24-li24wl.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=446&fit=crop&dpr=1 754w, https://images.theconversation.com/files/504369/original/file-20230113-24-li24wl.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=446&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/504369/original/file-20230113-24-li24wl.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=446&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Genetic lineage of COVID-19 subvariant XBB.1.5.</span>
<span class="attribution"><span class="source">(Sameer Elsayed)</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>How does XBB.1.5 differ from Omicron?</h2>
<p>XBB.1.5 is one of many Omicron subvariants of concern that have appeared on the global pandemic scene since the onset of the <a href="https://www.who.int/news-room/feature-stories/detail/one-year-since-the-emergence-of-omicron">first Omicron wave in November 2021</a>. In contrast to other descendants of the original Omicron variant (known as B.1.1.529), XBB.1.5 is a mosaic subvariant that <a href="https://doi.org/10.1007/s12291-022-01109-w">traces its roots to two Omicron subvariant lineages</a>. </p>
<p>XBB.1.5 is arguably the most genetically rich and <a href="https://www.scientificamerican.com/article/why-covids-xbb-1-5-kraken-variant-is-so-contagious/">most transmissible</a> SARS-CoV-2 Omicron subvariant yet. </p>
<h2>Where is XBB.1.5 prevalent?</h2>
<p><a href="https://www.who.int/docs/default-source/coronaviruse/11jan2023_xbb15_rapid_risk_assessment.pdf">According to the World Health Organization</a>, XBB.1.5 is circulating in at least 38 countries, with the highest prevalence in the United States, where it <a href="https://covid.cdc.gov/covid-data-tracker/#variant-proportions">accounts for approximately 43 per cent of COVID-19 cases nationwide</a>. Within the U.S., there is wide geographic variation in the proportion of cases caused by XBB.1.5, ranging from <a href="https://www.beckershospitalreview.com/public-health/xbb-1-5-prevalence-by-region.html">seven per cent in the Midwest to over 70 per cent in New England</a>. </p>
<p>XBB.1.5 has also been officially reported by governmental agencies in <a href="https://www.health.nsw.gov.au/Infectious/covid-19/Documents/weekly-covid-overview-20230107.pdf">Australia</a>, <a href="https://www.publichealthontario.ca/-/media/documents/ncov/epi/covid-19-sars-cov2-whole-genome-sequencing-epi-summary.pdf">Canada</a>, the <a href="https://www.ecdc.europa.eu/en/news-events/update-sars-cov-2-variants-ecdc-assessment-xbb15-sub-lineage">European Union</a>, <a href="https://www3.nhk.or.jp/nhkworld/en/news/20230112_36/">Japan</a>, <a href="https://www.kuna.net.kw/ArticleDetails.aspx?id=3077268&Language=en">Kuwait</a>, <a href="https://tass.com/world/1561313">Russia</a>, <a href="https://cov-spectrum.org/explore/Singapore/AllSamples/Past6M/variants?nextcladePangoLineage=xbb.1.5*&">Singapore</a>, <a href="https://www.nicd.ac.za/covid-19-update-xbb-1-5-variant/">South Africa</a> and the <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1128554/variant-technical-briefing-49-11-january-2023.pdf">United Kingdom</a>. <a href="https://outbreak.info/situation-reports?xmin=2022-07-13&xmax=2023-01-13&loc&pango=XBB.1&selected">Real-time surveillance data</a> reveals that XBB.1.5 is rapidly spreading across the globe and will likely become the next dominant subvariant.</p>
<p>XBB.1.5 has also been detected in municipal wastewater systems in the <a href="https://health.hawaii.gov/coronavirusdisease2019/files/2023/01/Wastewater-Report-01-03-23.pdf">United States</a>, <a href="https://thl.fi/en/web/thlfi-en/-/monitoring-wastewater-for-coronavirus-xbb-sublineage-of-omicron-variant-found-in-wastewater-follow-up-results-coming-in-january?redirect=%2Ffi%2Fajankohtaista%2Ftiedotteet-ja-uutiset%2Fkaikki-uutiset">Europe</a> and other places.</p>
<h2>How likely is XBB.1.5 to cause serious illness?</h2>
<figure class="align-center ">
<img alt="Illustration of five coronaviruses of different colours in a line" src="https://images.theconversation.com/files/504766/original/file-20230116-12-o1ah4n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/504766/original/file-20230116-12-o1ah4n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=217&fit=crop&dpr=1 600w, https://images.theconversation.com/files/504766/original/file-20230116-12-o1ah4n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=217&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/504766/original/file-20230116-12-o1ah4n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=217&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/504766/original/file-20230116-12-o1ah4n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=272&fit=crop&dpr=1 754w, https://images.theconversation.com/files/504766/original/file-20230116-12-o1ah4n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=272&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/504766/original/file-20230116-12-o1ah4n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=272&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The XBB lineage emerged following natural co-infection of a human host with two Omicron subvariants, namely BA.2.10.1 and BA.2.75.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>There is limited data about the ability of XBB.1.5 to cause serious illness. According to the <a href="https://www.who.int/docs/default-source/coronaviruse/11jan2023_xbb15_rapid_risk_assessment.pdf">World Health Organization</a>, XBB.1.5 does not have any specific mutations that make it any more dangerous than its ancestral subvariants. </p>
<p>Nonetheless, XBB.1.5 is perceived as being equally capable of causing serious illness in elderly and immunocompromised persons compared to previous Omicron subvariants of concern.</p>
<h2>Are current mRNA vaccines effective against XBB.1.5?</h2>
<p>XBB.1.5 and XBB.1 are the Omicron subvariants with the <a href="https://www.who.int/docs/default-source/coronaviruse/11jan2023_xbb15_rapid_risk_assessment.pdf">greatest immune-evasive properties</a>. Therefore, one of the most contentious issues surrounding XBB.1.5 relates to the degree of protection afforded by currently available mRNA vaccines, including the latest bivalent booster formulations. </p>
<p><a href="https://doi.org/10.1038/s41591-022-02162-x">Researchers from the University of Texas</a> determined that first-generation and bivalent mRNA booster vaccines containing BA.5 result in lacklustre neutralizing antibody responses against XBB.1.5. A report (yet to be peer reviewed) from investigators at the <a href="https://doi.org/10.1101/2022.12.17.22283625">Cleveland Clinic</a> found that bivalent vaccines demonstrate only modest (30 per cent) effectiveness in otherwise healthy non-elderly people when the variants in the vaccine match those circulating in the community. </p>
<p>Furthermore, some experts believe the administration of bivalent boosters for the prevention of COVID-19 illness in otherwise healthy young individuals is <a href="http://doi.org/10.1056/NEJMp2215780">not medically justified</a> nor <a href="https://doi.org/10.1136/jme-2022-108449">cost-effective</a>. </p>
<p>In contrast, <a href="http://doi.org/10.1056/NEJMc2214293">public health experts from Atlanta, Ga. and Stanford, Calif.</a> reported that although the neutralizing antibody activity of bivalent booster vaccines against XBB.1.5 is 12 to 26 times less than antibody activity against the wild-type (original) SARS-CoV-2 virus, bivalent vaccines still perform better than monovalent vaccines against XBB.1.5. </p>
<p>However, <a href="https://doi.org/10.1016/j.cell.2022.12.018">investigators from Columbia University</a> in New York found that neutralizing antibody levels following bivalent boosting were up to 155–fold lower against XBB.1.5 compared to levels against the wild-type virus following monovalent boosting. </p>
<p>This suggests that neither monovalent nor bivalent booster vaccines can be relied upon to provide adequate protection against XBB.1.5.</p>
<h2>How can you protect yourself against XBB.1.5?</h2>
<figure class="align-center ">
<img alt="A blue sign reading 'wearing a mask is recommended,' in French and English" src="https://images.theconversation.com/files/504744/original/file-20230116-18-xo2zgu.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/504744/original/file-20230116-18-xo2zgu.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=427&fit=crop&dpr=1 600w, https://images.theconversation.com/files/504744/original/file-20230116-18-xo2zgu.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=427&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/504744/original/file-20230116-18-xo2zgu.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=427&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/504744/original/file-20230116-18-xo2zgu.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=536&fit=crop&dpr=1 754w, https://images.theconversation.com/files/504744/original/file-20230116-18-xo2zgu.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=536&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/504744/original/file-20230116-18-xo2zgu.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=536&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Standard infection control precautions including indoor masking, social distancing and frequent handwashing are effective measures against XBB.1.5 and other subvariants of concern.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Graham Hughes</span></span>
</figcaption>
</figure>
<p>The rapid evolution of SARS-CoV-2 continues to pose a challenge for the management of COVID-19 illness using available preventive and therapeutic agents. Of note, all currently available monoclonal antibodies targeting the spike protein of SARS-CoV-2 are <a href="https://doi.org/10.1016/j.cell.2022.12.018">deemed to be ineffective against XBB.1.5</a>. </p>
<p>Antiviral medicines such as remdesivir and Paxlovid may be considered for the treatment of eligible infected patients at high risk of progressing to severe disease.</p>
<p>Standard infection control precautions including indoor masking, social distancing and frequent handwashing are effective measures that can be employed for personal and population protection against XBB.1.5 and other subvariants of concern.</p>
<p>Although bivalent boosters may be considered for elderly, immunocompromised and other risk-averse individuals, their effectiveness in preventing COVID-19 illness due to XBB.1.5 remains uncertain. </p>
<h2>Why is XBB.1.5 nicknamed ‘Kraken’?</h2>
<p><a href="https://www.mountainviewtoday.ca/amp/lifestyle-news/kraken-subvariant-name-beats-alphabet-soup-moniker-for-xbb15-biologist-6351664">Some scientists have coined unofficially-recognized nicknames for XBB.1.5</a> and other SARS-CoV-2 subvariants of concern, arguing that they are easier to remember than generic alphanumeric designations. </p>
<p><a href="https://news.uoguelph.ca/2023/01/biologist-makes-headlines-on-new-covid-subvariant/">The ‘Kraken’ label for XBB.1.5 is currently in vogue</a> on social media sites and news outlets, and the nicknames ‘Gryphon’ and ‘Hippogryph’ have been used to denote the ancestral subvariants XBB and XBB.1, respectively. <a href="https://www.merriam-webster.com/dictionary/kraken">Kraken</a> refers to a mythological Scandinavian sea monster or giant squid, Gryphon (or <a href="https://www.merriam-webster.com/dictionary/griffin">Griffin</a>) refers to a legendary creature that is a hybrid of an eagle and a lion, while Hippogryph (or <a href="https://www.merriam-webster.com/dictionary/hippogriff">Hippogriff</a>) is a fictitious animal hybrid of a Gryphon and a horse. </p>
<p>Notwithstanding their potential utility as memory aids, the use of nicknames or acronyms in formal scientific discussions should be avoided.</p><img src="https://counter.theconversation.com/content/197602/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sameer Elsayed does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The XBB.1.5 subvariant — nicknamed ‘Kraken’ — is arguably the most genetically rich and most transmissible SARS-CoV-2 Omicron subvariant yet.Sameer Elsayed, Professor of Medicine, Pathology & Laboratory Medicine, and Epidemiology & Biostatistics, Western UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1973632023-01-12T12:08:19Z2023-01-12T12:08:19ZCancer vaccine trials could start in the autumn – UK signs deal with BioNTech<figure><img src="https://images.theconversation.com/files/504038/original/file-20230111-4937-pkf525.jpg?ixlib=rb-1.1.0&rect=25%2C6%2C4255%2C2837&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/syringe-diferent-kind-ampoules-vials-close-2090699074">Mentor57/Shutterstock</a></span></figcaption></figure><p>The UK government <a href="https://www.gov.uk/government/news/new-partnership-to-boost-research-into-vaccines-for-cancer">recently announced</a> that it is partnering with German firm BioNTech to test vaccines for cancer and other diseases. The project aims to build on the mRNA vaccine technology that BioNTech became famous for developing, and which has been so successful at <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00320-6/fulltext">preventing serious illness and death from COVID</a>. </p>
<p>The goal of this new project is to deliver 10,000 personalised therapies to UK patients by 2030. With trials potentially starting as soon as this autumn.</p>
<p>Until recently, cancer has been treated with surgery (cutting out cancerous cells), radiotherapy (akin to burning cancer cells) and chemotherapy (stopping cancer cells from dividing by directly killing them). The latter is well-known for its harsh side-effects. In the last decade, though, we’ve seen the emergence of newer treatments, such as <a href="https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/what-is-immunotherapy.html">immunotherapy</a>. Immunotherapy usually works by blocking receptors (proteins with names such as CTLA-4, PD1 or PDL1) on the surface of cancer cells. </p>
<p>Our immune system already knows how to fight cancer, but these proteins are used by the cancer cells to turn the immune system off. By blocking these receptors, the immune system can recognise cancer as an enemy and kill it – like removing the cloak on an intruder.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/v9NBUeU3PG0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">How cancer immunotherapies work.</span></figcaption>
</figure>
<p>Although these drugs have their own side-effects, they’re usually much less severe than chemotherapy. And when they work, they can be continued for many months or even years. </p>
<p>Over a decade ago, scientists noticed that they work especially well <a href="https://pubmed.ncbi.nlm.nih.gov/20525992/">in melanomas</a>, an aggressive form of skin cancer. Since then, we have seen that they also work in <a href="https://www.cancerresearch.org/immunotherapy-by-cancer-type">many different cancers</a>, from lung cancer to bladder cancer, in cancers with lots of PDL1 on their surface, to those with many mutations in their DNA.</p>
<p>But they don’t work in every cancer and often don’t work at all. Like other cancer drugs, they can also work for some time, and then stop working.</p>
<h2>Recent success with mRNA cancer vaccine</h2>
<p>In December 2022, the drug companies Moderna and Merck <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/moderna-merck-vaccine-combo-cut-melanoma-recurrence-by-44-study-2022-12-13/">reported positive results</a> with a personalised cancer vaccine. The patients in the ongoing trial had stage 3 melanoma, meaning the cancer had spread to the lymph nodes near the cancer.</p>
<p>The normal course of action would be surgery to remove the tumour and surrounding lymph nodes and then give infusions of an anti-PD1 drug (typically Merck’s Keytruda).</p>
<p>In this new personalised vaccine approach, the scientists took the patients’ melanoma samples and looked at the letters in their DNA. They took up to 34 of the most mutated parts of the DNA, so-called neoantigens, and put them into a strand of mRNA – which can be thought of as the software in cells between the DNA (the hard drive) and the protein (the hardware). This mRNA was then given to patients as a personalised vaccine. It’s personalised because everyone has different neoantigens, so everyone in the study received slightly different vaccines with up to 34 different mutations encoded into just one strand of mRNA. </p>
<p>Just like the mRNA COVID vaccines, that mRNA made a little bit of the cancer inside the patients and their immune systems reacted against it to give them protection. </p>
<p>The results from this mid-stage study showed that the addition of the personalised cancer vaccine reduced the risk of the cancer returning (or death from the cancer) by 44% compared with the standard approach (surgery followed by anti-PD1 immunotherapy). And there were no extra side-effects over and above that of the existing immunotherapy.</p>
<p>While these results are potentially gamechanging, we need to see results in other cancers, in larger trials too. It’s incredibly exciting that one of the larger mRNA companies, BioNTech, is going to partner with the UK to develop a research hub in Cambridge, looking at these approaches and giving them to 10,000 patients on the NHS either routinely or in trials. </p>
<p>Advances in medicine are usually made in small steps, but this cancer vaccine – a new form of personalised, targeted medicine – could be a giant leap, just like the anti-PD1 or anti-PDL1 immunotherapies. It’s exciting that the UK will be central to that journey, to help turn cancer not only into a chronic disease we can live with but one we can cure.</p><img src="https://counter.theconversation.com/content/197363/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nothing to disclose.</span></em></p>The UK government announced that it is partnering with BioNTech to trial personalised cancer vaccines.Justin Stebbing, Professor of Biomedical Sciences, Anglia Ruskin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1907362022-09-25T20:03:31Z2022-09-25T20:03:31ZOmicron-specific vaccines may give slightly better COVID protection – but getting boosted promptly is the best bet<p>Vaccines (predominantly mRNA vaccines) have been our front-line defence against COVID and have <a href="https://www.medicalnewstoday.com/articles/covid-19-vaccines-saved-20-million-lives-in-1-year#Quantifying-the-lives-sa">saved millions of lives</a>.</p>
<p>Despite the emergence of genetically distinct COVID <a href="https://www.who.int/activities/tracking-SARS-CoV-2-variants/">variants</a> throughout the pandemic, we’ve relied on vaccines that target the spike protein from the virus originally detected in Wuhan, China. While still providing excellent protection, mRNA vaccines are less effective against newer variants with immunity waning <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2115481">within months of immunisation</a>.</p>
<p>Australia’s Omicron bivalent (two-strain) COVID vaccine has been <a href="https://www.health.gov.au/ministers/the-hon-mark-butler-mp/media/australias-first-bivalent-covid-19-vaccine-to-join-rollout">approved for use</a> and will be rolled out as stocks of the original vaccines need replacing. </p>
<p>While we hope they will provide better protection than existing vaccines, the little data we have so far suggests they only provide slightly better protection.</p>
<p>So, if you’re <a href="https://www.health.gov.au/initiatives-and-programs/covid-19-vaccines/getting-your-vaccination/booster-doses">eligible for your fourth dose</a>, it makes sense to get boosted with whichever COVID vaccine you’re offered now – rather than waiting until the Omicron-specific boosters enter circulation. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/better-covid-vaccines-are-on-the-way-what-do-they-do-and-what-technology-might-we-see-in-future-189531">Better COVID vaccines are on the way. What do they do? And what technology might we see in future?</a>
</strong>
</em>
</p>
<hr>
<h2>Playing catch up with new variants</h2>
<p>One key technological advance with mRNA vaccines is the ability to modify the mRNA sequence that encodes the spike protein in SARS-CoV-2 (the virus that causes COVID). This means scientists can target the viral spike protein and respond to the viral variants currently circulating. </p>
<p>But it still takes time to manufacture a recalibrated mRNA vaccine, then test it, distribute it and get it into people’s arms. </p>
<p>Earlier in the pandemic, Moderna produced a bivalent vaccine that also targeted the Beta variant. Initial lab tests <a href="https://www.nature.com/articles/s41591-021-01527-y">showed</a> boosting with this variant-specific vaccine increased antibodies against Beta approximately two times better than the boost provided by the original vaccine.</p>
<p>However development was discontinued because Beta was replaced by other COVID variants. </p>
<p>As long as SARS-CoV-2 evolves, keeping up with it is going to remain a challenge for variant-specific vaccines. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-were-on-a-global-panel-looking-at-the-staggering-costs-of-covid-17-7m-deaths-and-counting-here-are-11-ways-to-stop-history-repeating-itself-190658">We were on a global panel looking at the staggering costs of COVID – 17.7m deaths and counting. Here are 11 ways to stop history repeating itself</a>
</strong>
</em>
</p>
<hr>
<h2>Testing new vaccines now</h2>
<p>So how do scientists determine if bivalent vaccines work better than existing vaccines? </p>
<p>The gold standard is a clinical trial that assesses protection from disease. Early in the pandemic when few people had immunity to SARS-CoV-2, this was relatively straight forward. Starting with a baseline of no immunity makes it easier to design a trial to assess the protection provided by vaccines. </p>
<p>The situation is a lot more complicated now, with much of the world’s population vaccinated, previously infected or both – often multiple times. </p>
<p>Measuring relative effectiveness in a clinical trial comparing two vaccines in such a diverse population exposed to unpredictable waves of infection requires large numbers of study participants – and lots of time and money. </p>
<p>As an alternative, we can examine indicators of protection. Antibodies are generated by the immune system when we’re exposed to the SARS-CoV-2 spike protein, either via vaccination or infection. The aim is to generate lots of antibodies that bind to the surface of the spike protein and stop the virus infecting cells. </p>
<p>Scientists can recruit study participants who know their vaccination and infection history and take their baseline antibody levels. Then they can be boosted with either the standard mRNA vaccine or the variant-modified bivalent vaccine. The level of virus-neutralising antibodies in the blood can then be assessed in the lab after boosting. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1571659947246751744"}"></div></p>
<h2>How effective is the Omicron booster?</h2>
<p>The Moderna COVID bivalent booster targets the ancestral virus and Omicron BA.1 subvariant. It has been <a href="https://www.health.gov.au/news/atagi-statement-on-use-of-the-moderna-bivalent-originalomicron-vaccine">approved for use</a> in Australia and will be rolled out when our stocks of existing Moderna boosters have been exhausted. </p>
<p>The bivalent vaccine will then be offered to adults who are due to have their third or fourth doses. </p>
<p><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2208343">Lab-based studies</a> assessing antibody responses suggest the bivalent vaccine offers 1.5 to 2 times improved immunity over the boost provided by the original vaccine.</p>
<p>However, it’s unclear how much better they will be than existing boosters at protecting people from disease, particularly given BA.1 has been replaced by Omicron sub-variants. These have <a href="https://www.nature.com/articles/s41586-022-04980-y">several mutations</a> that distinguish them from BA.1 and so the bivalent Omicron vaccine is no longer a perfect match. </p>
<p>To try and understand vaccine effectiveness in the absence of a dedicated clinical trial, researchers can model the relationship between lab-based antibody studies and previous clinical trials to predict how well new vaccines will protect from disease. </p>
<p>This <a href="https://www.medrxiv.org/content/10.1101/2022.08.25.22279237v1">type of analysis</a> shows the original vaccine is quite good at restoring protection against disease caused by different variants when given as a booster. </p>
<p>Variant-modified vaccines such as the newly approved Omicron booster are predicted to improve that by 5–10%, depending on the variant and level of existing immunity. This might seem like a small improvement but it could mean additional lives saved. </p>
<p>That said, you are at much greater risk of disease if it has been several months since your last booster. That’s why it’s best to get boosted as soon as you’re eligible, rather than waiting for an Omicron-specific booster.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1549830290687885312"}"></div></p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/even-mild-covid-raises-the-chance-of-heart-attack-and-stroke-what-to-know-about-the-risks-ahead-190552">Even mild COVID raises the chance of heart attack and stroke. What to know about the risks ahead</a>
</strong>
</em>
</p>
<hr>
<h2>What might come next for the vaccine rollout?</h2>
<p>The government has accepted the Australian Technical Advisory Group on Immunisation (ATAGI) advice to wait until current Moderna booster stocks run out before putting the bivalent Omicron boosters into circulation. </p>
<p>This seems like the right call, given the Omicron boosters probably offer only a modest improvement in protection against the Omcicron sub-variants currently circulating. </p>
<p>In the future we might see annual COVID boosters adapted to the currently circulating strains or predicted strains, like season flu shots. There appears to be a desire to do this in the United States with the Federal Drug Administration fast-tracking authorisation of booster mRNA vaccines that target the Omicron BA.4/BA.5 subvariants, before data is available on <a href="https://www.nbcnews.com/health/health-news/fda-authorizes-pfizers-modernas-updated-covid-booster-shots-rcna44825">how well they work</a>.</p>
<p>Rather than constantly updating COVID vaccines, an alternative approach is to develop a “variant-proof” vaccine that targets multiple SARS-CoV-2 variants. We could combine this with treatments like <a href="https://theconversation.com/nasal-covid-19-vaccines-help-the-body-prepare-for-infection-right-where-it-starts-in-your-nose-and-throat-183790">nose sprays</a> that stimulate immunity against a range of viruses. </p>
<p>For now, bivalent vaccines work as well, if not a little better, than the original vaccines so transitioning to them makes sense.</p><img src="https://counter.theconversation.com/content/190736/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nathan Bartlett does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>As the virus that causes COVID evolves, keeping up with it remains a challenge for variant-specific vaccines. The booster you can get now is the best one to get.Nathan Bartlett, Associate Professor, School of Biomedical Sciences and Pharmacy, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1908262022-09-22T12:40:17Z2022-09-22T12:40:17ZWhen should you get the new COVID-19 booster and the flu shot? Now is the right time for both<figure><img src="https://images.theconversation.com/files/485731/original/file-20220920-16871-cf9dvv.jpg?ixlib=rb-1.1.0&rect=140%2C60%2C6569%2C4386&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It is safe to get the newly formulated COVID-19 booster shot and the flu shot at the same time.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/close-up-photo-female-nurse-giving-vaccine-to-woman-royalty-free-image/1361778753?adppopup=true">SDI Productions/ E+ via Getty Images</a></span></figcaption></figure><p>At this point in the COVID-19 pandemic, nearly everyone has experienced the panic and uncertainty that come with having mild COVID-like symptoms – such as a cough and sore throat – only to test negative day after day. With cold and flu season just around the corner, that state of frustrating uncertainty is likely to strike most of us again. </p>
<p>Both COVID-19 and the flu are contagious respiratory illnesses that have <a href="https://www.cdc.gov/flu/symptoms/flu-vs-covid19.htm">similar symptoms</a>, making it difficult to distinguish between the two viral infections without a lab test. Testing is the only way to know which virus is causing your symptoms. In fact, labs are working to create one test that can detect <a href="https://doi.org/10.1001/jama.2022.11031">both COVID-19 and the flu</a>. </p>
<p>As a <a href="https://hhs.purdue.edu/directory/elizabeth-libby-richards/">nursing professor</a> with <a href="https://scholar.google.com/citations?user=Pdh4gSgAAAAJ&hl=en&oi=ao">experience in public health promotion</a>, I am often asked about the differences between the flu and COVID-19. This year I am fielding many questions about the timing of getting the new COVID-19 booster and the flu shot and whether they can be given together.</p>
<h2>Parsing the symptoms</h2>
<p>Symptoms of both COVID-19 and the flu can range from mild – or no noticeable symptoms at all – to severe. While flu infection does not typically affect one’s ability to taste or smell, <a href="https://my.clevelandclinic.org/health/symptoms/16708-loss-of-taste-and-smell">loss of taste or smell</a> has been a common symptom associated with COVID-19 infection. Both infections can cause fevers, chills, body aches and fatigue. More severe symptoms of either infection include difficulty breathing and subsequent infections like pneumonia. </p>
<p>During the 2021-2022 flu season, <a href="https://www.washingtonpost.com/health/2022/01/05/flurona-coronavirus-flu-symptoms/">the term “flurona”</a> made its way into the COVID-19 vernacular. Flurona refers to a simultaneous infection with both the flu and COVID-19. While only a few cases of co-infections <a href="https://doi.org/10.3389/fmed.2021.681469">have been reported</a>, it would not be surprising to see more of them this coming flu season. Vaccination for both the flu and COVID-19 is your best protection against both.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/JV4WmFSQwmk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">What flurona is – and isn’t.</span></figcaption>
</figure>
<h2>Timing the shots</h2>
<p>With the <a href="https://theconversation.com/will-omicron-specific-booster-shots-be-more-effective-at-combating-covid-19-5-questions-answered-189610">newly formulated COVID-19 booster shot</a> now available and flu season just around the corner, a natural question is whether there is an optimal timing for the two shots.</p>
<p>The answer to that question is to get both as soon as possible. It is important to consider that it takes approximately two weeks after vaccination for the body to develop antibodies from both the <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html">COVID-19 vaccines</a> and the <a href="https://www.cdc.gov/flu/prevent/keyfacts.htm">flu vaccine</a>. </p>
<p>As long as you have completed your primary COVID-19 vaccine series and it has been at least eight weeks since your last COVID-19 booster, now is the time to <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-to-date.html?">get the updated COVID-19 vaccine</a> that targets both the original strain of SARS-CoV-2 – the virus that causes COVID-19 – and the most recent omicron subvariants. The original COVID-19 vaccines and booster series have dramatically reduced the <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7023e2.htm">number of COVID-19 infection and death rates</a>, as well as <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7112e1.htm">cases of severe COVID-19</a> that lead to hospitalization. </p>
<p>While everyone 6 months of age and older are recommended to receive both the COVID-19 and flu vaccines, certain populations have a higher risk for severe infection, such as <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html">pregnant women</a>, and should be extra vigilant about getting vaccinated. </p>
<p>Further, among those vaccinated against COVID-19, symptoms during an infection <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/breakthrough-infections-coronavirus-after-vaccination#">tend to be milder</a>. However, due in part to the quickly evolving nature of the virus, it’s become clear that immune protection from COVID-19 vaccination or infection does not last forever. While studies show that the primary COVID-19 series maintains efficacy against severe disease and death six months after vaccination, protection against infection decreases by between <a href="https://doi.org/10.1016/S0140-6736(22)00152-0">20% to 30% by six months</a> after vaccination. </p>
<p>This decline in immune protection is exactly <a href="https://www.yalemedicine.org/news/covid-19-booster">why booster shots are so critical</a>. Without a large uptake of <a href="https://theconversation.com/low-vaccine-booster-rates-are-now-a-key-factor-in-covid-19-deaths-and-racial-disparities-in-booster-rates-persist-187272">booster shots in the population</a>, COVID-19 infection rates could surge again.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/UyheqSbbZGA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The updated COVID-19 booster shots are now available.</span></figcaption>
</figure>
<p>Timing is also important with the flu vaccine. Flu cases typically begin to rise in October and peak between December and February, <a href="https://www.cdc.gov/flu/about/season/flu-season.htm">but can last through May</a>. Ideally, people should get vaccinated before flu begins to spread, making <a href="https://www.cdc.gov/flu/season/faq-flu-season-2022-2023.htm">September or early October</a> the ideal flu vaccination time. </p>
<h2>A difficult flu season ahead</h2>
<p>Due to lockdowns, reduced travel, school closures and mask mandates in the first and second years of the pandemic, both the <a href="https://www.cdc.gov/flu/about/burden/past-seasons.html">2020-2021 and 2021-2022 flu seasons</a> were estimated to have fewer hospitalizations and deaths from the flu compared to many of the pre-pandemic years. </p>
<p>In the fall of 2021, experts became concerned about the potential for a <a href="https://theconversation.com/flu-season-paired-with-covid-19-presents-the-threat-of-a-twindemic-making-the-need-for-vaccination-all-the-more-urgent-169011">COVID-19 and flu “twindemic,”</a> especially as COVID-19 restrictions were lifting and masks were coming off. Fortunately, the worst didn’t bear out – flu numbers in the 2021-2022 season did not return to pre-pandemic levels. However, the possibility of a “twindemic” is not out of the picture for the coming flu season.</p>
<p>Flu seasons are <a href="https://www.cdc.gov/flu/about/burden/faq.htm">inherently difficult to predict</a>. With most people traveling again, schools open, mask mandates lifted and workers headed back to the office, people are undoubtedly going to be exposed to germs that they have been more protected from for the last two and a half years. </p>
<p>To further compound this, flu vaccine rates <a href="https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-dashboard.html#">have been lower during the pandemic</a>, suggesting that Americans may be out of the habit of getting their annual flu shot. </p>
<h2>Pairing the shots</h2>
<p>Many are also wondering whether they can or should get both the updated COVID-19 booster and the flu shot at the same time. The good news is, <a href="https://www.cdc.gov/flu/season/faq-flu-season-2022-2023.htm">yes, it is safe</a> for both adults and children 12 years of age and up who are eligible for the updated COVID-19 booster to get these vaccines simultaneously. </p>
<p>A recent study found that common vaccine side effects such as pain at the injection site <a href="https://doi.org/10.1001/jamanetworkopen.2022.22241">occurred at slightly higher rates</a> when someone received the flu vaccine and a COVID-19 vaccine at the same time, as opposed to receiving only a COVID-19 booster. However, those reactions, including fatigue and headache, were mild and resolved within a day or two.</p>
<p>You don’t need to make two separate vaccine visits as long as you are due for your next COVID-19 shot. However, I don’t recommend waiting to get your flu shot if you are not yet due for a COVID-19 booster. The Centers for Disease Control and Prevention suggests everyone receive their flu vaccine by <a href="https://www.cdc.gov/flu/season/faq-flu-season-2022-2023.htm">the end of October</a>. But if you miss that deadline, it is absolutely better to get vaccinated later in the season than not at all.</p>
<h2>Community matters too</h2>
<p>Getting the flu and COVID-19 vaccines isn’t just about your own health, it’s about family and community health too. Communities with higher vaccination rates have <a href="https://theconversation.com/what-is-herd-immunity-a-public-health-expert-and-a-medical-laboratory-scientist-explain-170520">fewer opportunities to spread the virus</a>. </p>
<p>Keep in mind <a href="https://www.cdc.gov/flu/prevent/whoshouldvax.htm">that many people cannot be vaccinated</a> because they have weakened immune systems or are undergoing treatments. They depend on those around them for protection. While one person may experience mild symptoms if they contract the flu or COVID-19, they could spread the virus to others who could become severely ill. Because it’s impossible to predict how people will react if they get sick, getting the flu and COVID-19 vaccines is the best prevention strategy.</p><img src="https://counter.theconversation.com/content/190826/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Libby Richards has received funding from the National Institutes of Health. She is is affiliated with the American Public Health Association. </span></em></p>When COVID-19 and the flu co-infect, it’s ‘flurona.’ But such cases are rare, and there are effective ways to protect yourself from both viruses.Libby Richards, Associate Professor of Nursing, Purdue UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1906012022-09-19T18:01:33Z2022-09-19T18:01:33ZCanadian scientists made life-saving contributions during the COVID-19 pandemic<figure><img src="https://images.theconversation.com/files/485134/original/file-20220916-9898-2fmj80.jpg?ixlib=rb-1.1.0&rect=134%2C0%2C4857%2C2814&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Funding research is essential to meet future health challenges.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/canadian-scientists-made-life-saving-contributions-during-the-covid-19-pandemic" width="100%" height="400"></iframe>
<p>This year, the Nobel Prize in physiology or medicine will be awarded on Oct. 3. Canada will be in the spotlight again, thanks to Canadian scientists’ involvement with mRNA vaccine development. </p>
<p>The Canada Gairdner International Award, offered to five researchers who have excelled in the medical sciences, is often considered a predictor of the Nobel Prize.</p>
<p>Earlier this year, the Gairdner Foundation recognized <a href="https://biochem.ubc.ca/person/pieter-cullis/">molecular biologist Pieter Cullis</a>, <a href="https://www.pennmedicine.org/providers/profile/katalin-kariko">biochemist Katalin Karikó</a> and <a href="https://www.med.upenn.edu/apps/faculty/index.php/g275/p20322">physician-researcher Drew Weissman</a>. Cullis was recognized <a href="https://doi.org/10.1016/j.cell.2022.03.026">for the lipid nanoparticle packaging of the mRNA designed by Karikó and Weissman</a> for the COVID-19 vaccine.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/22op-qa7xBc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The 2022 Canada Gairdner International Awards.</span></figcaption>
</figure>
<h2>mRNA vaccine development</h2>
<p>Canada’s input into the development of functional mRNA vaccines also includes Nahum Sonenberg, <a href="https://www.mcgill.ca/gci/article/sante-gala-road-rna-therapies">a pioneer of mRNA research</a> who was consulted in the development of Moderna’s mRNA vaccine. Sonenberg received a <a href="https://gairdner.org/award_winners/nahum-sonenberg/">Gairdner International Award in 2008</a> for discovering how mRNA is constructed with a cap and tail to enable protein synthesis. </p>
<p>Moderna was itself co-founded by <a href="https://www.utoronto.ca/news/u-t-alumnus-derrick-rossi-proud-play-role-promising-covid-19-vaccine-toronto-star">Derrick Rossi, who attended the University of Toronto</a>, and <a href="https://mcgillnews.mcgill.ca/s/1762/news/interior.aspx?gid=2&pgid=2347">Noubar Afeyan, who attended McGill University</a>.</p>
<h2>Adenovirus vaccines</h2>
<p>In 2021, in addition to <a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/authorization/applications.html">approving the mRNA vaccines from BioNTech and Moderna</a>, Canada also approved the Oxford vaccine. This vaccine uses an adenovirus to insert the gene for the COVID-19 virus spike protein, which stimulates an immune response that protects against COVID-19.</p>
<p><a href="https://brighterworld.mcmaster.ca/articles/analysis-how-the-puzzle-of-viral-vector-vaccines-was-solved-leading-to-todays-covid-19-shots/">Molecular biologist Frank Graham</a> pioneered the use of adenovirus to generate vaccines.</p>
<p>Research has estimated that <a href="https://doi.org/10.1016/S1473-3099(22)00320-6">19.8 million lives were saved by the vaccines in 2021</a>, including over 310,000 lives in Canada alone.</p>
<h2>Undervaluing the importance of research</h2>
<p>The recognition of exceptional scientists by the Nobel Prize committee is sadly not a value shared by our federal government today. In 2017, then <a href="http://www.sciencereview.ca/eic/site/059.nsf/eng/home">Minister of Science Kirsty Duncan</a> highlighted the need for increased funding to the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Social Sciences and Humanities Research Council (SSHRC) to reverse the decline in Canadian research. </p>
<p>In 2017, CIHR funding was only 2.5 per cent of that of the corresponding National Institutes of Health (NIH) in the United States. By 2022, CIHR funding was proportionally less, at <a href="https://cihr-irsc.gc.ca/e/52798.html">2.3 per cent</a> of that of the <a href="https://www.aip.org/fyi/2022/nih-budget-fy22-outcomes-and-fy23-request">NIH</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1392118457861386241"}"></div></p>
<p>The U.S. recognizes the importance of research by investing five times more per capita than Canada in health research. As each federal budget is announced, Canadian scientists await eagerly for an increase in budgets to internationally competitive levels which never comes.</p>
<p>The discrepancy between Canada and our peer countries in the G7 and the Organisation for Economic Co-operation and Development means that <a href="https://www.timeshighereducation.com/news/large-surpluses-post-lockdown-blip-say-canadian-universities">our future scientists will look elsewhere for promising, unobstructed careers</a>. </p>
<p>Losing our scientists will have an effect on the health of Canadians and the economy.</p>
<h2>Science literacy</h2>
<p>During the pandemic, Canadians have been following updates and news regarding public health messaging that affects their everyday lives. We have observed and scrutinized how scientific research is conducted and communicated.</p>
<p>The pandemic seems to have sparked a thirst and curiosity for science. The more people inform themselves, the more they are protected from false information which could harm them and their loved ones.</p>
<p>Never has there been a greater need to promote the relevance of science to all across Canada and especially our federal and provincial decision-makers.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-cant-canada-win-another-nobel-prize-in-medicine-87910">Why can't Canada win another Nobel Prize in medicine?</a>
</strong>
</em>
</p>
<hr>
<p>The COVID-19 pandemic opened our eyes to the fact that Canada was unprepared. From the <a href="https://doi.org/10.1038/s41586-020-2012-7">first sequencing of the SARS-CoV-2 viral RNA</a> to the <a href="https://www.england.nhs.uk/2020/12/landmark-moment-as-first-nhs-patient-receives-covid-19-vaccination/">first vaccination</a>, the rapid response from scientists demonstrated why scientific research is so relevant to all. With multiple health threats, investing in research should no longer be seen as a luxury.</p>
<h2>Global competition</h2>
<p>As seemingly uncontrollable inflation and the problems of the hard-hit economy take hold, <a href="https://www.theglobeandmail.com/canada/article-student-scientists-demand-action-on-federal-scholarships/">Canada’s current and future scientists will be gravely affected by the lack of funding to support labs</a>. Without increased investment into scientific research, <a href="https://montrealgazette.com/opinion/opinion-montreal-aids-conference-steeped-in-legacy-and-hope">Canada will not be able to compete scientifically</a>. This plight is a threat to Canada’s health and its economy.</p>
<p>Canada needs to retain, recruit and support talent to meet future challenges. These will come from several sources, including future pandemics, <a href="https://theconversation.com/gutter-to-gut-how-antimicrobial-resistant-microbes-journey-from-environment-to-humans-189446">increased antibiotic resistance to bacterial infections</a>, the growing impact of cancer, age-related diseases and, of course diabetes. Indeed, it was the discovery of insulin that represented <a href="https://www.nobelprize.org/prizes/medicine/1923/summary/">our first Nobel Prize in Physiology or Medicine in 1923</a>.</p>
<p>Research saves lives.</p>
<p><em>John Bergeron gratefully acknowledges Kathleen Dickson as co-author.</em></p><img src="https://counter.theconversation.com/content/190601/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Bergeron does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Canadian scientists have made significant contributions during the pandemic response, including vital roles in developing COVID-19 vaccines. But underfunding puts the future of science in Canada at risk.John Bergeron, Emeritus Robert Reford Professor and Professor of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1896102022-09-01T12:25:45Z2022-09-01T12:25:45ZWill omicron-specific booster shots be more effective at combating COVID-19? 5 questions answered<figure><img src="https://images.theconversation.com/files/482134/original/file-20220831-4878-mt0k59.jpg?ixlib=rb-1.1.0&rect=53%2C116%2C6000%2C3853&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In a matter of days, eligible people will be lining up to receive the newly formulated booster shot.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/vaccination-center-royalty-free-image/1358994941?adppopup=true">filadendron/E+ via Getty Images</a></span></figcaption></figure><p><em>On Sept. 1, 2022, the Centers for Disease Control and Prevention <a href="https://www.cdc.gov/media/releases/2022/s0901-covid-19-booster.html">endorsed the use of updated COVID-19 booster shots</a> that are specifically tailored to combat the two most prevalent <a href="https://doi.org/10.1136/bmj.o1969">omicron subvariants, BA.4 and BA.5</a>. The decision comes just a day after the <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-bivalent-covid-19-vaccines-use">Food and Drug Administration’s emergency use authorization of the shots</a>. The CDC’s backing will enable a full roll-out of the reformulated vaccines to begin within days.</em> </p>
<p><em>The new booster shots – one by Moderna and another from Pfizer-BioNTech – come as more than <a href="https://www.nytimes.com/interactive/2021/us/covid-cases.html">450 people are still dying of COVID-19 every day in the U.S</a>.</em> </p>
<p><em>As of Aug. 31, 2022, only <a href="https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-people-additional-dose-totalpop">48.5% of booster-eligible people in the U.S. have received their first booster shot</a>, and just under 34% of those eligible have received their second. These low numbers may in part be influenced by <a href="https://theconversation.com/should-you-get-a-covid-19-booster-shot-now-or-wait-until-fall-two-immunologists-help-weigh-the-options-184809">people waiting for the newer versions of the vaccines</a> to provide better protection. But booster shots have proven to be an <a href="https://theconversation.com/low-vaccine-booster-rates-are-now-a-key-factor-in-covid-19-deaths-and-racial-disparities-in-booster-rates-persist-187272">essential layer of protection against COVID-19</a>.</em> </p>
<p><em><a href="https://scholar.google.com/citations?user=jJVj3sUAAAAJ&hl=en">Prakash Nagarkatti</a> and <a href="https://scholar.google.com/citations?user=af7TahQAAAAJ&hl=en">Mitzi Nagarkatti</a> are immunologists who study infectious disorders and how vaccines trigger different aspects of the immune system to fight infection. They weigh in on how the updated booster shots train the immune system and how protective they might be against COVID-19.</em> </p>
<h2>1. What is different about the updated booster shots?</h2>
<p>The newly authorized shots are the first updates to the original COVID-19 vaccines that were introduced in late 2020. They use the same <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">mRNA technology as the original vaccines</a>. The key difference between the original COVID-19 shots and the new “bivalent” version is that the latter consists of a mixture of mRNA that encodes the <a href="https://doi.org/10.1038/s41401-020-0485-4">spike proteins</a> of both the original SARS-CoV-2 virus and the more <a href="https://doi.org/10.1136/bmj.o1969">recent omicron subvariants, BA.4 and BA.5</a>.</p>
<p>As of late August 2022, the BA.4 and BA.5 omicron subvariants are dominant worldwide. <a href="https://covid.cdc.gov/covid-data-tracker/#variant-proportions">In the U.S., currently</a> 89% of COVID-19 infections are caused by BA.5 and 11% are caused by BA.4.</p>
<p>The inability of the original vaccine strains to prevent reinfection and <a href="https://theconversation.com/how-long-does-protective-immunity-against-covid-19-last-after-infection-or-vaccination-two-immunologists-explain-177309">to trigger long-term protective immunity</a> prompted the need for the reformulated vaccines.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/vZeTs9-rgPU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The booster shots target the BA.4 and BA.5 subvariants of the omicron variant, as well as the original version of SARS-CoV-2, the virus that causes COVID-19.</span></figcaption>
</figure>
<h2>2. How does a bivalent vaccine trigger an immune response?</h2>
<p>In an actual COVID-19 infection, the SARS-CoV-2 virus uses its protruding <a href="https://doi.org/10.1073/pnas.2003138117">spike protein to latch onto human cells</a> and gain entry into cells. The spike protein triggers the production of so-called <a href="https://doi.org/10.1126/science.abd7728">neutralizing antibodies</a>, which bind to the spike protein and prevent the virus from invading other cells.</p>
<p>But <a href="https://doi.org/10.3390%2Fv14030640">when the virus mutates</a>, as we know that it does, the antibodies that were previously produced in response to the virus can no longer effectively bind to the newly mutated spike protein. In this respect, the SARS-CoV-2 virus acts like a chameleon – a master of disguise – by changing its body configuration and escaping recognition by the immune system. </p>
<p>The ongoing viral mutations are why antibodies produced in response to the original vaccine strains have over time become less effective at fending off infections by new variants.</p>
<p>The concept of bivalent vaccines aimed at protecting against two different strains of a virus is not new. For instance, <a href="https://www.fda.gov/vaccines-blood-biologics/vaccines/cervarix">Cervarix is an FDA-approved bivalent vaccine</a> that provides protection against two different types of human papillomaviruses that cause cancer.</p>
<h2>3. How protective will the new shots be against infection?</h2>
<p>There are as of yet no human studies on the efficacy of the new bivalent vaccine at preventing reinfections and providing long-term immune protection.</p>
<p>However, in human clinical trials and laboratory studies, <a href="https://doi.org/10.1126/science.ade6584">both Pfizer-BioNTech and Moderna found</a> that their initial version of the bivalent vaccine, which was directed against the original SARS-CoV-2 virus and an earlier omicron strain, BA.1, induced a strong immune response and longer protection against both the original strain and the BA.1 variant. In addition, the companies reported that the same early combination generated a significant antibody response against the newest omicron subvariants, BA.4 and BA.5, though this antibody response was lower than that seen against subvariant BA.1.</p>
<p>Based on those results, in spring 2022 the <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-recommends-inclusion-omicron-ba45-component-covid-19-vaccine-booster">FDA rejected</a> the BA.1 bivalent boosters because the agency felt the boosters may fall short of providing sufficient protection against the newest strains, BA.4 and BA.5, which were by then spreading quickly throughout the U.S. and the world. So the FDA asked Pfizer-BioNTech and Moderna <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/fda-recommends-inclusion-ba4-ba5-subvariants-covid-boosters-2022-06-30/">to develop bivalent vaccines specifically targeting BA.4 and BA.5</a>, instead of BA.1. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1561732830211735553"}"></div></p>
<p>Because clinical trials are time-consuming, the <a href="https://www.npr.org/sections/health-shots/2022/08/18/1117778748/whats-behind-the-fdas-controversial-strategy-for-evaluating-new-covid-boosters">FDA was willing to consider animal studies</a> and other laboratory findings, such as the ability of antibodies to neutralize the virus, to decide whether to authorize the bivalent boosters. </p>
<p>This decision <a href="https://www.npr.org/sections/health-shots/2022/08/18/1117778748/whats-behind-the-fdas-controversial-strategy-for-evaluating-new-covid-boosters">has stirred up controversy</a> over whether it is appropriate for the FDA to approve a booster without direct human data to support it. However, the FDA has stated that millions of people have safely received the mRNA vaccines – which were originally tested in humans – and that the changes in the mRNA sequences in the vaccines <a href="https://abcnews.go.com/Health/fall-covid-19-boosters-roll-pending-green-light/story?id=88973334">do not affect vaccine safety</a>. Thus, it concluded that the bivalent vaccines are safe and that there is no need to wait for human clinical trials.</p>
<p>It is also noteworthy that influenza vaccines are introduced each year based on prediction of the strain that is likely to be dominant, <a href="https://doi.org/10.1126/science.ade6584">and such formulations do not undergo new clinical trials</a>. </p>
<p>Based on available evidence from the previous COVID-19 vaccines, we believe it is very likely that the new boosters will continue to offer strong protection from <a href="https://www.cdc.gov/media/releases/2022/s0318-COVID-19-vaccines-protect.html">severe COVID-19 leading to hospitalization and death</a>.
But whether they will protect against reinfection and breakthrough infections remains to be seen. </p>
<h2>4. Will it only be a booster shot?</h2>
<p>The bivalent vaccines <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-bivalent-covid-19-vaccines-use">can only be used</a> as a booster shot at least two months after the completion of the primary series – or initial required shots – or following a previous booster shot. The Moderna bivalent vaccine is authorized for use in people 18 years of age, while the Pfizer bivalent vaccine is authorized for those 12 years of age and older. </p>
<p>Because of the superiority of the bivalent vaccines, the FDA has also removed the use authorization for the original monovalent Moderna and Pfizer COVID-19 vaccines for booster purposes in individuals 18 years of age and older and 12 years of age and older, respectively. </p>
<p>The new <a href="https://doi.org/10.1126/science.ade6584">bivalent vaccines contain a lower dose of mRNA</a>, and as such are meant to be used only as boosters and not in people who have never received a COVID-19 vaccination. </p>
<h2>5. Will the new shots protect against future variants?</h2>
<p>How well the bivalent vaccines will perform in the face of new variants that might arise will depend on the nature of future spike protein mutations. </p>
<p>If it is a minor mutation or set of mutations when compared to the original strain or to omicron variants BA.4 and BA.5, the new shots will provide good protection. However, if a hypothetical new strain were to possess highly unique mutations in its spike protein, then it’s likely that it could once again dodge immune protection. </p>
<p>On the flip side, the successful development of the updated vaccines demonstrates that the mRNA vaccine technology is nimble and innovative enough that – within a couple of months of the emergence of a new variant – it is now likely possible to develop and distribute new vaccines that are tailor-made to fight an emerging variant.</p>
<p><em>This article has been updated to reflect the CDC’s endorsement of the reformulated shots.</em></p><img src="https://counter.theconversation.com/content/189610/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prakash Nagarkatti receives funding from the National Institutes of Health and the National Science Foundation.</span></em></p><p class="fine-print"><em><span>Mitzi Nagarkatti receives funding from the National Institutes of Health.</span></em></p>The CDC’s endorsement of the reformulated COVID-19 booster shots represents a major step in the effort to get more Americans boosted.Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaMitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1812352022-06-05T12:22:00Z2022-06-05T12:22:00ZWe still need a vaccine patent waiver, but not the one on offer at the World Trade Organization meeting<figure><img src="https://images.theconversation.com/files/466910/original/file-20220603-17-5nwz4k.jpg?ixlib=rb-1.1.0&rect=382%2C238%2C4930%2C3241&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Global Justice campaigners in London stand by fake coffins to highlight global COVID-19 deaths. If pharma companies waived intellectual property rights, it would be easier for low- and middle-income countries to access COVID-19 vaccines.
</span> <span class="attribution"><span class="source">(AP Photo/Alastair Grant)</span></span></figcaption></figure><p>In mid-June, the <a href="https://www.wto.org/english/thewto_e/minist_e/mc12_e/mc12_e.htm">World Trade Organization (WTO) will meet</a> to finish negotiations to waive certain sections of the agreement on Trade Related Intellectual Property Rights (TRIPS). However, it is not the TRIPS waiver originally proposed 18 months ago by member states South Africa and India, which would have allowed countries to produce lower-cost generic vaccines and other COVID-19 medical tools without the risk of legal trade challenges.</p>
<p>The opposition to the waiver from a few WTO member states — home to the pharma companies holding monopoly patent rights over the vaccines — has resulted in “<a href="https://doi.org/10.1016/S0140-6736(22)00328-2">vaccine apartheid</a>” (rich countries buying up all the early supplies) and “<a href="https://www.thenation.com/article/economy/pfizer-pandemic-profiteering/">vaccine profiteering</a>” (companies making multi-billion-dollar profits and fighting every effort to allow generic competition). </p>
<p>Vaccine supply is no longer the main issue. Pharma companies still holding the vaccine patents can now produce enough for everyone — though not necessarily at affordable prices — and have described the <a href="https://healthpolicy-watch.news/with-covid-vaccine-supply-outstripping-vaccination-rates-pharma-giants-question-pursuit-of-ip-waiver/">idea of a TRIPS waiver now as “insane” and “unproductive</a>.” </p>
<p>But for the scores of WTO member states and thousands of global health researchers still supporting the waiver <a href="https://theconversation.com/covid-19-drug-and-vaccine-patents-are-putting-profit-before-people-149270">(myself included)</a>, getting the WTO to approve one at its upcoming June ministerial meeting remains important. Just not the waiver that’s on the negotiating table. </p>
<h2>Worse than no waiver</h2>
<p><a href="https://www.wto.org/english/news_e/news22_e/trip_06may22_e.htm">The current version</a> is the outcome of discussions involving the two original proposing members, the United States and the European Union. It is restricted to vaccines — a U.S. request — ignoring, for now at least, therapeutics, diagnostics and other essential COVID-19-related health products. </p>
<figure class="align-center ">
<img alt="Hands holding a syringe and vial of vaccine" src="https://images.theconversation.com/files/466905/original/file-20220603-15469-2mn4y6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/466905/original/file-20220603-15469-2mn4y6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/466905/original/file-20220603-15469-2mn4y6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/466905/original/file-20220603-15469-2mn4y6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/466905/original/file-20220603-15469-2mn4y6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/466905/original/file-20220603-15469-2mn4y6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/466905/original/file-20220603-15469-2mn4y6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The waiver under negotiation puts a time limit on the waived obligations.</span>
<span class="attribution"><span class="source">(AP Photo/Michel Euler)</span></span>
</figcaption>
</figure>
<p>It requires generic manufacturers to identify all related patents, which is impossible given vaccines’ complex “<a href="https://doi.org/10.1007/s10551-021-04873-6">patent thickets</a>” (overlapping patent rights), and something not required under present TRIPS rules. It puts a time limit on the waived obligations, as though pandemics are calendar-savvy. </p>
<p>While it removes barriers to generic companies exporting to developing countries that lack their own manufacturing capacity, it excludes countries that supplied more than 10 per cent of global vaccine exports in 2021, namely, China. </p>
<p>A shadow of its original intent, the new waiver is <a href="https://twn.my/title2/wto.info/2022/ti220514.htm">endorsed only by the EU, with support from the WTO director-general</a>. </p>
<h2>Why the new waiver proposal should be opposed</h2>
<p>If enacted as currently drafted, the new waiver sets a precedent that will restrict the ability of countries with the capacity to mass produce therapeutics, diagnostics and even personal protective equipment. This would apply to the still-with-us COVID-19 pandemic and for any new zoonotic outbreaks that are <a href="https://theconversation.com/future-infectious-diseases-recent-history-shows-we-can-never-again-be-complacent-about-pathogens-177746">almost certainly on the near horizon</a>. </p>
<p>Without a meaningful waiver, new variant-ready vaccines <a href="https://medicalxpress.com/news/2022-04-pfizer-eyes-covid-vaccine-variants.html">expected later this year</a> are likely to be gobbled up once more by high-paying rich countries, with the poorer ones left with older less-effective versions. </p>
<figure class="align-center ">
<img alt="Vials of vaccine with purple caps shot from above" src="https://images.theconversation.com/files/466908/original/file-20220603-9439-4opry1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/466908/original/file-20220603-9439-4opry1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/466908/original/file-20220603-9439-4opry1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/466908/original/file-20220603-9439-4opry1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/466908/original/file-20220603-9439-4opry1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/466908/original/file-20220603-9439-4opry1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/466908/original/file-20220603-9439-4opry1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Pharma companies holding patents can now produce enough vaccine for everyone, though not necessarily at affordable prices.</span>
<span class="attribution"><span class="source">(AP Photo/Achmad Ibrahim)</span></span>
</figcaption>
</figure>
<p>The same scenario applies to therapeutics such as <a href="https://www.bloomberg.com/news/articles/2022-04-22/covid-antiviral-pills-seen-surging-after-slow-initial-uptake">Pfizer’s antiviral drug, Paxlovid</a>. Most of its current supply will go to wealthy countries that can afford the high prices Pfizer charges. Pfizer will allow licences for generic versions to be produced for distribution to 95 developing countries, but not until 2023. </p>
<p>Moderna, the other mRNA vaccine leader, is busy <a href="https://www.aljazeera.com/opinions/2022/3/16/modernas-profits-show-why-big-pharma-cant-meet-our-health-needs">registering patents for its vaccine in South Africa</a> as that country, with WTO support, is close to copying Moderna’s recipe, the know-how for which it plans to share publicly. Moderna’s new patents could <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/moderna-patent-application-raises-fears-africa-covid-vaccine-hub-2022-02-17/">jeopardize this effort</a>. The company meanwhile has plans to create its own mRNA plant in Kenya to supply the African continent <a href="https://socialeurope.eu/control-the-vampire-companies">on its own profitable terms</a>. </p>
<p>On May 25, Pfizer announced that it would eventually provide all “<a href="https://www.weforum.org/agenda/2022/05/pfizer-launches-an-accord-for-a-healthier-world-a-call-for-action-to-improve-health-equity-globally/?utm_source=sfmc&utm_medium=email&utm_campaign=2778051_Am22-AgendaDaily-26May2022&utm_term=&emailType=Agenda%20Week">current and future patent-protected medicines on a not-for-profit basis” to 45 lower-income countries</a>, beginning with five countries in Africa. </p>
<p>The company’s decision is welcome, but questions remain. Will Pfizer forego lucrative sales of its current and future drugs to rich countries in order to supply (eventually) the 1.2 billion people living in the world’s poorest nations? Or will these countries have to wait until the paying world’s 6.7 billion people have had their supply needs met? </p>
<h2>Current property rights not fit for global health purpose</h2>
<p>The bottom line: for-profit companies should not be setting public health policy during global health emergencies. Individual corporate decisions to supply life-saving health innovations at cost in otherwise unprofitable markets is not a sustainable or ethical solution. </p>
<p>Bluntly stated: companies’ intellectual property rights should not be allowed to trump people’s health rights. </p>
<figure class="align-center ">
<img alt="A crowd outdoors with people holding blue signs reading 'Support patent waivers on COVID-19 vaccines'" src="https://images.theconversation.com/files/466911/original/file-20220603-11-mv11bv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/466911/original/file-20220603-11-mv11bv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=417&fit=crop&dpr=1 600w, https://images.theconversation.com/files/466911/original/file-20220603-11-mv11bv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=417&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/466911/original/file-20220603-11-mv11bv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=417&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/466911/original/file-20220603-11-mv11bv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=524&fit=crop&dpr=1 754w, https://images.theconversation.com/files/466911/original/file-20220603-11-mv11bv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=524&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/466911/original/file-20220603-11-mv11bv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=524&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Activists support patent waivers on COVID-19 vaccines in front of the European Union office during an EU summit in Kyiv, Ukraine, on Oct. 12, 2021.</span>
<span class="attribution"><span class="source">(AP Photo/Efrem Lukatsky)</span></span>
</figcaption>
</figure>
<p>Investment into new health products means taking risks, and it warrants some reward. However, much of the groundwork in pharmaceutical research is publicly funded. </p>
<p>This was certainly the case with COVID-19 vaccines, and one of the reasons why many organizations argued that these discoveries <a href="https://peoplesvaccine.org/">should be considered “people’s vaccines” and treated as public goods</a>. Governments need to place <a href="https://www.who.int/publications/m/item/governing-health-innovation-for-the-common-good">conditions on the financial support they give to health research</a> to ensure that the results are more equitably shared. </p>
<p>In the case of public health emergencies, such as pandemics, this should include requirements that companies forego their monopoly property rights, accept negotiated royalties for their efforts and share their knowledge. </p>
<p>President Joe Biden’s administration recently took a step in this direction. It <a href="https://www.hhs.gov/about/news/2022/05/12/nih-licenses-covid-19-research-tools-early-stage-technologies-who-program.html">licensed 11 COVID-19 inventions</a> that arose from in-house research at the National Institutes of Health, including early-stage development of the stabilized spike protein that forms the base of mRNA vaccines. </p>
<p>Described as “<a href="https://www.science.org/content/article/pretty-big-deal-u-s-makes-covid-19-technologies-available-use-developing-countries">a pretty big deal</a>” by an advocate of shared intellectual property, the licenses will be administered by the non-profit <a href="https://medicinespatentpool.org/">Medicines Patent Pool</a> that negotiates low royalty costs for generic manufacturers, so inventors will still get some reward. </p>
<p>But this early-stage knowledge-sharing is insufficient to enable full development of medical innovations, which requires drug companies holding patents on the finished, commercialized vaccines and COVID-19-related technologies to waive these rights and to share their technical know-how. </p>
<h2>Canada and the June WTO meeting</h2>
<p>As with the rest of the world, Canada’s attention is moving away from COVID-19 to <a href="https://www.cbc.ca/news/business/canada-inflation-april-1.6457520">inflation fears</a> and <a href="https://theconversation.com/why-did-russia-invade-ukraine-faqs-about-the-conflict-that-has-shocked-the-world-177963">Russia’s war against Ukraine</a>. With surprisingly little media coverage, the government began holding <a href="https://www.ourcommons.ca/Committees/en/FAAE/StudyActivity?studyActivityId=11504514">parliamentary committee hearings on vaccine equity</a> this past spring. Still, it remains uncommitted on the waiver, as it has since the original waiver was proposed. </p>
<figure class="align-center ">
<img alt="A globe and a syringe against a blue background" src="https://images.theconversation.com/files/466903/original/file-20220603-26-bpuy54.jpg?ixlib=rb-1.1.0&rect=748%2C30%2C3341%2C2501&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/466903/original/file-20220603-26-bpuy54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/466903/original/file-20220603-26-bpuy54.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/466903/original/file-20220603-26-bpuy54.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/466903/original/file-20220603-26-bpuy54.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/466903/original/file-20220603-26-bpuy54.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/466903/original/file-20220603-26-bpuy54.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Companies’ intellectual property rights should not be allowed to trump people’s health rights.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Health and civil society groups, meanwhile, remain committed to urging the government to make the right ethical and health protective decision. They are calling on Canada to <a href="https://policyalternatives.ca/newsroom/updates/canada-should-reject-compromise-proposal-trips-waiver-its-present-form-civil">use the June WTO meeting to bring the deeply flawed new waiver proposal closer to the original one</a>. </p>
<p>There is still a need for a decent TRIPS waiver to ensure that intellectual property rights do not get in the way of rapid and equitable access to medicines or any other essential health innovations. That must be one of the key lessons we take from our COVID-19 experience.</p><img src="https://counter.theconversation.com/content/181235/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ronald Labonte receives funding from the Canadian Institutes of Health Research, and is a member of the Steering Council of the People's Health Movement, which advocates for global health equity.</span></em></p>Waiving patent rights on COVID-19 vaccines and drugs is still crucial to ensure access globally, but the waiver on the table at the June World Trade Organization meeting doesn’t do the job.Ronald Labonte, Professor and Distinguished Research Chair, Globalization and Health Equity, L’Université d’Ottawa/University of OttawaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1817912022-05-23T15:50:44Z2022-05-23T15:50:44ZWhat happened to the AstraZeneca vaccine? Now rare in rich countries, it’s still saving lives around the world<figure><img src="https://images.theconversation.com/files/464504/original/file-20220520-24-o2874g.jpg?ixlib=rb-1.1.0&rect=8%2C0%2C2986%2C1998&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/bangkok-thailand-march-22-2021-new-1942294513">PhotobyTawat/Shutterstock</a></span></figcaption></figure><p>The AstraZeneca vaccine, developed in partnership with the University of Oxford, was one of the <a href="https://theconversation.com/oxford-covid-vaccine-authorised-in-the-uk-global-health-expert-on-why-this-is-a-key-moment-152533">first vaccines available</a> for use in the UK and around the world during the COVID pandemic. </p>
<p>More than <a href="https://www.astrazeneca.com/media-centre/press-releases/2021/two-billion-doses-of-astrazenecas-covid-19-vaccine-supplied-to-countries-across-the-world-less-than-12-months-after-first-approval.html">two billion doses</a> have been distributed to at least 170 countries, with around <a href="https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting">50 million doses</a> administered in the UK. </p>
<p>But most of those were first and second doses – only a little over <a href="https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting">56,000 doses</a> of AstraZeneca had been given as booster doses as of May 2022. The vast majority of third doses administered in the UK have been Pfizer (30.1 million doses) and Moderna (9.4 million). </p>
<p>So despite being an excellent vaccine, the use of AstraZeneca in the UK has declined across the pandemic. It’s also not used much elsewhere in Europe, or in the US where it has <a href="https://www.ft.com/content/e1edb2b2-0e12-4c83-9257-eeeb2ba29267">yet to be approved</a>.</p>
<p>The reason for its limited use in high-income countries could be a combination of two factors. First, it’s likely that the mRNA vaccines (specifically those manufactured by Pfizer and Moderna) are perceived to be even more effective than AstraZeneca. And second, the vaccine’s <a href="https://www.science.org/doi/10.1126/science.371.6536.1294">reputation</a> took a hit when some people who received this vaccine subsequently developed blood clots. </p>
<p>On the first point, some research has indicated the mRNA vaccines offer slightly <a href="https://www.nejm.org/doi/full/10.1056/nejmoa2108891">higher levels of protection</a> against previously dominant variants, including delta. A <a href="https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003991">2022 study</a> from the Netherlands that measured antibody levels against SARS-CoV-2 following vaccination showed Pfizer and Moderna performed better than the viral vector vaccines (including AstraZeneca). But one caveat here is that the participants who received the mRNA vaccines were much younger than the AstraZeneca recipients. Immune responses typically <a href="https://www.nature.com/articles/s41586-021-03739-1">wane faster</a> in older populations.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-valneva-covid-vaccine-has-been-approved-for-use-in-the-uk-heres-what-the-evidence-says-181378">The Valneva COVID vaccine has been approved for use in the UK – here's what the evidence says</a>
</strong>
</em>
</p>
<hr>
<p>The public fallout from the blood clot scares, associated with AstraZeneca but not with Pfizer or Moderna, also affected the vaccine’s rollout. The vaccine is still licensed for use in younger adults in the UK, who were deemed to be at higher risk of blood clots following the AstraZeneca vaccine. However, the UK’s Joint Committee on Vaccination and Immunisation <a href="https://www.gov.uk/government/publications/use-of-the-astrazeneca-covid-19-vaccine-jcvi-statement-7-may-2021/use-of-the-astrazeneca-covid-19-azd1222-vaccine-updated-jcvi-statement-7-may-2021">recommended</a> that people aged 39 and under should be offered an alternative to AstraZeneca where possible.</p>
<p>These adverse events gained significant media coverage, and public confidence in the AstraZeneca vaccine was certainly knocked in the UK and beyond. For example, in April 2021, <a href="https://www.bbc.co.uk/news/world-europe-56744474">Denmark</a> became the first European country to cease using the vaccine, with <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/norway-will-not-use-astrazeneca-covid-19-vaccine-says-daily-vg-2021-05-12/">Norway</a> following soon after. Around the same time, several Canadian provinces temporarily <a href="https://www.forbes.com/sites/ginaheeb/2021/03/29/canadian-panel-recommends-pausing-astrazeneca-vaccine-for-55-and-younger/">suspended</a> the AstraZeneca vaccine for people under 55 as a precautionary measure. All of this came amid high levels of COVID in these countries and elsewhere, and at a time when global demand for COVID vaccines greatly outstripped supply. </p>
<p>These somewhat kneejerk reactions made waves further afield. For example, <a href="https://figshare.com/articles/thesis/Examining_drivers_of_COVID-19_vaccine_hesitancy_in_Ghana/14494851">research</a> my colleagues and I conducted in Ghana highlighted how people had observed the responses in Europe and North America. The result was increased hesitancy towards the AstraZeneca vaccine. </p>
<p>Despite all this, the UK’s Medicines and Healthcare products Regulatory Agency, the European Medicines Agency and the World Health Organization <a href="https://www.bbc.co.uk/news/world-europe-56440139">continued</a> at all times to recommend the vaccine, based on its safety and effectiveness record. </p>
<figure class="align-center ">
<img alt="A woman receives a vaccination from a health worker dressed in PPE." src="https://images.theconversation.com/files/464529/original/file-20220520-23-on209d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/464529/original/file-20220520-23-on209d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/464529/original/file-20220520-23-on209d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/464529/original/file-20220520-23-on209d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/464529/original/file-20220520-23-on209d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/464529/original/file-20220520-23-on209d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/464529/original/file-20220520-23-on209d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Public confidence in the AstraZeneca vaccine has suffered.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/male-doctor-vaccine-young-woman-patient-1915528687">Sabrina Bracher/Shutterstock</a></span>
</figcaption>
</figure>
<h2>An important vaccine for the developing world</h2>
<p>The proportion of the Ghanaian population that has received <a href="https://ourworldindata.org/coronavirus/country/ghana">one or more doses</a> of any COVID vaccine is just over 30%. Our <a href="https://figshare.com/articles/preprint/Examining_predictors_of_vaccine_uptake_and_hesitancy_in_three_rural_sub-municipalities_in_Nkwanta_South_Oti_region_Ghana/19360988">2022 research</a> in Ghana indicates that vaccine hesitancy rates among those currently unvaccinated ranges between 30%-50%, depending on the population surveyed. </p>
<p>An April 2022 briefing by the Ghana Health Service (not published online) indicated that 43% of the 28 million doses received in Ghana have been AstraZeneca. Of the vaccines administered in March 2022, 57% were AstraZeneca. </p>
<p>Among the reasons for a preference for AstraZeneca, there will be <a href="https://theconversation.com/why-the-oxford-astrazeneca-vaccine-is-now-a-global-gamechanger-150660">considerations</a> around supply, cost and logistical issues. For example, the vaccine requires only regular refrigerator storage, compared with the mRNA vaccines which need to be frozen. For these reasons the AstraZeneca vaccine is vital for Ghana, along with many other lower-income countries. High local and global confidence is essential to ensure a successful vaccination campaign with high uptake. </p>
<p>The UK and many other high-income countries are likely to continue predominantly using mRNA COVID vaccines. However, much of the knowledge we have around “which vaccine is better” relates to previous variants rather than omicron. As the virus continues to evolve, so must the evidence base. </p>
<p>There is an increasing body of evidence that “<a href="https://www.nature.com/articles/d41586-021-02853-4">mixing and matching</a>” vaccine types is safe and effective, and may even generate stronger or broader immune responses over time. In this light, there could be a role for AstraZeneca or other vaccines such as <a href="https://theconversation.com/novavax-covid-vaccine-is-nearing-approval-but-what-impact-will-it-have-171647">Novavax</a>, alongside mRNA vaccines. </p>
<p>In the longer term, we need a <a href="https://cepi.net/news_cepi/cepi-partners-with-bionet-to-expand-variant-proof-vaccine-programme/">vaccine</a> that can protect against multiple variants or even all coronaviruses.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/omicron-may-reach-millions-before-vaccines-do-but-that-doesnt-mean-race-to-vaccinate-the-world-is-over-174492">Omicron may reach millions before vaccines do – but that doesn't mean race to vaccinate the world is over</a>
</strong>
</em>
</p>
<hr>
<p>For many high-income countries in 2022, the mRNA vaccines are the vaccine of choice, rather than AstraZeneca. The mRNA vaccines are also being manufactured in sufficiently large volumes to make supply much <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/covax-vaccine-supply-outstrips-demand-first-time-2022-02-23/">less of an issue</a> than it was earlier in the pandemic. These are all important factors for national decision-makers. However, it’s important to emphasise that the AstraZeneca vaccine is a safe and effective product, and remains a vital tool to underpin the global response to the pandemic.</p><img src="https://counter.theconversation.com/content/181791/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Head has received funding from the Bill & Melinda Gates Foundation and the UK Department for International Development. </span></em></p>Despite being an excellent vaccine, the use of AstraZeneca in the UK has declined over the course of the COVID pandemic.Michael Head, Senior Research Fellow in Global Health, University of SouthamptonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1800092022-05-04T18:02:21Z2022-05-04T18:02:21ZNanoparticles are the future of medicine – researchers are experimenting with new ways to design tiny particle treatments for cancer<figure><img src="https://images.theconversation.com/files/461078/original/file-20220503-38813-i2h2zm.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nanoparticles can help cancer drugs home in on tumors and avoid damaging healthy cells.
</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/destruction-of-a-cancer-cell-illustration-royalty-free-illustration/713780459">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p>When you hear the word “nanomedicine,” it might call to mind scenarios like those in the 1966 movie “<a href="https://www.youtube.com/watch?v=dO5E4wkg0hA">Fantastic Voyage</a>.” The film portrays a medical team shrunken down to ride a microscopic robotic ship through a man’s body to clear a blood clot in his brain. </p>
<p>Nanomedicine has not reached that level of sophistication yet. Although scientists can generate nanomaterials smaller then several nanometers – the “nano” indicating one-billionth of a meter – today’s nanotechnology has not been able to generate functional electronic robotics tiny enough to inject safely into the bloodstream. But since the <a href="https://doi.org/10.1038/nnano.2006.115">concept of nanotechnology</a> was first introduced in the 1970s, it has made its mark in many everyday products, including electronics, fabrics, food, water and air treatment processes, cosmetics and drugs. Given these successes across different fields, many medical researchers were eager to use nanotechnology to diagnose and treat disease.</p>
<p>I am a <a href="https://scholar.google.com/citations?user=Ufab1aYAAAAJ&hl=en">pharmaceutical scientist</a> who was inspired by the promise of nanomedicine. <a href="https://pharmacy.umich.edu/sun-lab">My lab</a> has worked on developing cancer treatments using nanomaterials over the past 20 years. While nanomedicine has seen many successes, some researchers like me have been disappointed by its <a href="https://doi.org/10.1016/j.jconrel.2019.05.044">underwhelming overall performance</a> in cancer. To better translate success in the lab to treatments in the clinic, we proposed a <a href="https://doi.org/10.1021/acsnano.9b09713">new way to design</a> cancer drugs using nanomaterials. Using this strategy, we <a href="https://www.science.org/doi/10.1126/scitranslmed.abl3649">developed a treatment</a> that was able to achieve full remission in mice with metastatic breast cancer. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/APTItoAnKEs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">While nanomedicine isn’t “Fantastic Voyage,” it shares the film’s treatment goal of delivering a drug exactly where it needs to go.</span></figcaption>
</figure>
<h2>What is nanomedicine?</h2>
<p><a href="https://doi.org/10.1021/acsnano.9b09713">Nanomedicine</a> refers to the use of materials at the nanoscale to diagnose and treat disease. Some researchers define nanomedicine as encompassing any medical products using nanomaterials smaller than 1,000 nanometers. Others more narrowly use the term to refer to injectable drugs using nanoparticles smaller than 200 nanometers. Anything larger may not be safe to inject into the bloodstream.</p>
<p>Several nanomaterials have been successfully used in vaccines. The most well-known examples today are the <a href="https://doi.org/10.1016/j.ijpharm.2021.120586">Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines</a>. These vaccines used a nanoparticle made of of lipids, or fatty acids, that helps carry the mRNA to where it needs to go in the body to trigger an immune response.</p>
<p>Researchers have also successfully used nanomaterials in diagnostics and medical imaging. <a href="https://www.fda.gov/media/145080/download">Rapid COVID-19 tests</a> and <a href="https://doi.org/10.1016/s1028-4559(08)60127-8">pregnancy tests</a> use gold nanoparticles to form the colored band that designates a positive result. <a href="https://doi.org/10.1186/s13244-019-0771-1">Magnetic resonance imaging, or MRI</a>, often uses nanoparticles as contrast agents that help make an image more visible.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/QorK2X7GsVU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Gold is one type of nanoparticle whose uses researchers are testing in a range of contexts.</span></figcaption>
</figure>
<p>Several nanoparticle-based drugs have been approved for cancer treatment. <a href="https://doi.org/10.1016/j.jconrel.2012.03.020">Doxil (doxorubicin)</a> and <a href="https://dx.doi.org/10.4172%2F2157-7439.1000164">Abraxane (paclitaxel)</a> are chemotherapy drugs that use nanomaterials as a delivery mechanism to improve treatment efficacy and reduce side effects.</p>
<h2>Cancer and nanomedicine</h2>
<p>The potential of nanomedicine to improve a drug’s effectiveness and reduce its toxicity is attractive for cancer researchers working with anti-cancer drugs that often have strong side effects. Indeed, <a href="https://doi.org/10.1016/j.jconrel.2020.07.007">65% of clinical trials using nanoparticles</a> are focused on cancer.</p>
<p>The idea is that nanoparticle cancer drugs could <a href="https://doi.org/10.1021/acsnano.9b09713">act like biological missiles</a> that destroy tumors while minimizing damage to healthy organs. Because tumors have leaky blood vessels, researchers believe this would allow nanoparticles to <a href="https://dx.doi.org/10.1021%2Facs.bioconjchem.6b00437">accumulate in tumors</a>. Conversely, because nanoparticles can circulate in the bloodstream longer than traditional cancer treatments, they could accumulate less in healthy organs and reduce toxicity. </p>
<p>Although these design strategies have been successful in mouse models, most nanoparticle cancer drugs have <a href="https://doi.org/10.1021/acsnano.9b09713">not been shown</a> to be more effective than other cancer drugs. Furthermore, while some nanoparticle-based drugs can reduce toxicity to certain organs, they may increase toxicity in others. For example, while the nanoparticle-based <a href="https://doi.org/10.1007/s13577-012-0057-0">Doxil</a> decreases damage to the heart compared with other chemotherapy options, it can increase the risk of developing <a href="https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/hand-foot-syndrome-or-palmar-plantar-erythrodysesthesia">hand-foot syndrome</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/b3hWEC553sU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The COVID-19 mRNA vaccines spurred excitement about nanoedicine’s potential applications to other diseases.</span></figcaption>
</figure>
<h2>Improving nanoparticle-based cancer drugs</h2>
<p>To investigate ways to improve how nanoparticle-based cancer drugs are designed, my research team and I <a href="https://doi.org/10.1016/j.biomaterials.2021.120910">examined how well</a> five approved nanoparticle-based cancer drugs accumulate in tumors and avoid healthy cells compared with the same cancer drugs without nanoparticles. Based on the findings of our lab study, we proposed that designing nanoparticles to be <a href="https://doi.org/10.1021/acsnano.9b09713">more specific</a> to their intended target could improve their translation from animal models to people. This includes creating nanoparticles that address the shortcomings of a particular drug – such as common side effects – and home in on the types of cells they should be targeting in each particular cancer type.</p>
<p>[<em>Get fascinating science, health and technology news.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-fascinating">Sign up for The Conversation’s weekly science newsletter</a>.]</p>
<p>Using these criteria, we designed a <a href="https://www.science.org/doi/10.1126/scitranslmed.abl3649">nanoparticle-based immunotherapy</a> for metastatic breast cancer. We first identified that breast cancer has a type of immune cell that suppresses immune response, helping the cancer become resistant to treatments that stimulate the immune system to attack tumors. We hypothesized that while drugs could overcome this resistance, they are unable to sufficiently accumulate in these cells to succeed. So we designed nanoparticles made of a common protein called albumin that could deliver cancer drugs directly to where these immune-suppressing cells are located.</p>
<p>When we tested our nanoparticle-based treatment on mice genetically modified to have breast cancer, we were able to eliminate the tumor and achieve complete remission. All of the mice were still alive 200 days after birth. We’re hopeful it will eventually translate from animal models to cancer patients.</p>
<h2>Nanomedicine’s bright but realistic future</h2>
<p>The success of some drugs that use nanoparticles, such as the <a href="https://doi.org/10.1038/d41586-021-02483-w">COVID-19 mRNA vaccines</a>, has prompted excitement among researchers and the public about their potential use in treating various other diseases, including talks about a future <a href="https://doi.org/10.1038/d41573-021-00110-x">cancer vaccine</a>. However, a vaccine for an infectious disease is <a href="https://doi.org/10.1186/s12943-021-01335-5">not the same</a> as a vaccine for cancer. Cancer vaccines may require different strategies to overcome treatment resistance. Injecting a nanoparticle-based vaccine into the bloodstream also has different design challenges than injecting into muscle.</p>
<p>While the field of nanomedicine has made good progress in getting drugs or diagnostics out of the lab and into the clinic, it still has a long road ahead. Learning from past successes and failures can help researchers develop breakthroughs that allow nanomedicine to live up to its promise.</p><img src="https://counter.theconversation.com/content/180009/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Duxin Sun receives funding from NIH, FDA and Pharmaceutical Industries for his lab research at The University of Michigan. </span></em></p>The COVID-19 mRNA vaccines put nanomedicine in the spotlight as a potential way to treat diseases like cancer and HIV. While the field isn’t there yet, better design could help fulfill its promise.Duxin Sun, Professor of Pharmaceutical Sciences, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1819262022-05-04T12:33:24Z2022-05-04T12:33:24ZWill new vaccines be better at fighting coronavirus variants? 5 questions answered<figure><img src="https://images.theconversation.com/files/461072/original/file-20220503-24-26xibt.jpg?ixlib=rb-1.1.0&rect=63%2C34%2C3190%2C2008&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Dozens of coronavirus vaccines are in clinical trials in the U.S.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coronavirus-vaccine-vials-on-a-laboratory-shelf-royalty-free-image/1301805656?adppopup=true">Joao Paulo Burini/Moment via Getty Images</a></span></figcaption></figure><p><em>The first three coronavirus vaccines earned Emergency Use Authorization more than a year ago. To date, no other vaccines have been put into use in the U.S – but that will soon change. <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">More than 40 vaccines are undergoing clinical trials</a> in the U.S., employing a number of different approaches to protecting people from the coronavirus. <a href="https://scholar.google.com/citations?user=TyYJ1hkAAAAJ&hl=en&oi=ao">Vaibhav Upadhyay</a> and <a href="https://pharmacy.cuanschutz.edu/about-us/profile/krishna-mallela">Krishna Mallela</a> have been studying the coronavirus spike protein since the outbreak of the pandemic and are developing COVID-19 therapeutics. Together, they explain what vaccines are in development and why some of the vaccines should be better than what’s available now.</em></p>
<h2>1. Why are companies working on new vaccines?</h2>
<p>A major reason why new vaccines are important – and why the world is still dealing with COVID-19 – is the continued emergence of <a href="https://theconversation.com/what-are-covid-19-variants-and-how-can-you-stay-safe-as-they-spread-a-doctor-answers-5-questions-163697">new variants</a>. Most of the differences between variants are <a href="https://theconversation.com/will-omicron-the-new-coronavirus-variant-of-concern-be-more-contagious-than-delta-a-virus-evolution-expert-explains-what-researchers-know-and-what-they-dont-169020">changes in the spike protein</a>, which is on the surface of the virus and helps it enter and infect cells. </p>
<p>Some of these small changes in the spike protein have allowed the coronavirus to <a href="https://theconversation.com/will-omicron-the-new-coronavirus-variant-of-concern-be-more-contagious-than-delta-a-virus-evolution-expert-explains-what-researchers-know-and-what-they-dont-169020">infect human cells more efficiently</a>. These changes have also made it so that previous vaccinations or infections with COVID-19 <a href="https://doi.org/10.1038/s41586-021-04385-3">provide less protection against the new variants</a>. Updated or new vaccines could be better at detecting these different spike proteins and better at protecting against new variants.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A number of vaccine vials on a production line." src="https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Vaccines fall generally into four categories: whole virus vaccines, viral vector vaccines, protein-based vaccines and nucleic acid-based vaccines.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/covid-19-vaccine-production-line-royalty-free-image/1290225107?adppopup=true">Andriy Onufriyenko/Moment via Getty Images</a></span>
</figcaption>
</figure>
<h2>2. What kinds of vaccines are in the works?</h2>
<p>So far, <a href="https://covid19.trackvaccines.org/">38 vaccines have been approved around the world</a>, and the U.S. has approved three of those. There are <a href="https://covid19.trackvaccines.org/">currently 195 vaccine candidates</a> at different stages of development worldwide, out of which <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">41 are in clinical trials in U.S.</a> Vaccines against SARS-CoV-2 can be broadly divided into four classes: whole virus, viral vector, protein-based and nucleic acid-based vaccines. </p>
<p>Whole virus vaccines generate immunity using a complete, though weakened – called inactivated or attenuated – SARS-CoV-2 virus. Currently there are two of these vaccines in clinical trials in the U.S. Viral vector vaccines are a variation on this approach. Instead of using the whole coronavirus, they use a modified version of a <a href="https://theconversation.com/how-does-the-johnson-and-johnson-vaccine-compare-to-other-coronavirus-vaccines-4-questions-answered-155944">harmless adenovirus that carries parts of the coronavirus spike protein</a>. The Johnson & Johnson vaccine is a viral vector vaccine, and there are <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">15 more candidates in this category in clinical trials in the U.S.</a>.</p>
<p>Protein-based vaccines use just the spike protein or part of the spike protein to generate immunity. Since the spike protein is one of the most functionally important parts of the coronavirus, an immune response that just targets this one part is sufficient to prevent or overcome an infection. The U.S. currently has <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">five protein-based vaccines undergoing clinical trials</a>.</p>
<p>Nucleic acid-based vaccines are currently the most widely used in the U.S. These are made of genetic material, like DNA or RNA, that <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">codes for the coronavirus’ spike protein</a>. Once a person gets one of these shots, their body reads the genetic material and produces the spike protein. This in turn generates an immune response. There are <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">17 RNA and two DNA vaccines in clinical trials in the U.S.</a> Some of these are using the genetic material from newer variants, including updated versions of the Moderna and Pfizer vaccines.</p>
<h2>3. Will new vaccines be better than existing ones?</h2>
<p>The Moderna, Pfizer and J&J vaccines are based on the original strain of the coronavirus and are <a href="https://doi.org/10.1016/j.cell.2021.03.013">less potent when facing new variants</a>. Vaccines based on new variants would provide better protection against those newer strains than existing vaccines, and some are under development. Nucleic acid-based vaccines <a href="https://theconversation.com/how-can-scientists-update-coronavirus-vaccines-for-omicron-a-microbiologist-answers-5-questions-about-how-moderna-and-pfizer-could-rapidly-adjust-mrna-vaccines-172943">are the easiest to update</a> and make up the majority of variant-targeted vaccines. Moderna has already produced a vaccine that <a href="https://www.cnbc.com/2022/04/19/moderna-redesigned-covid-vaccine-produced-stronger-immunity-against-omicron-than-current-shots.html">contains mRNA from both the beta and omicron variants</a>, and some recently published clinical data shows that it is more effective against newer variants than Moderna’s original shot.</p>
<p>While updating nucleic acid vaccines is important, some research suggests that viral vector or whole virus vaccines could be <a href="https://doi.org/10.1016/j.vaccine.2021.08.018">more effective against new variants – without the need for updating</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A model of the coronavirus." src="https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Whole virus vaccines use an inactivated, harmless version of the coronavirus – seen here – to produce a strong immune response.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Coronavirus._SARS-CoV-2.png#/media/File:Coronavirus._SARS-CoV-2.png">Alexey Solodovnikov, Valeria Arkhipova via WikimediaCommons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>4. What are the advantages of whole virus vaccines?</h2>
<p>Nucleic acid-based and protein-based vaccines use only the spike protein to produce an immune response. With a whole virus vaccine, the immune system not only recognizes the spike protein, but all other parts of the coronavirus, too. The other parts of the virus help to quickly generate a strong immune response that involves many different <a href="https://doi.org/10.1038/s41541-021-00292-w">branches of the immune system and lasts a long time</a>.</p>
<p>Another benefit of whole virus and viral vector vaccines is the ease of storage and shipping. Viral vector vaccines can be <a href="https://doi.org/10.1016/j.biologicals.2014.05.007">stored in common household refrigerators</a> for months, sometimes years. By comparison, the Moderna and Pfizer mRNA vaccines must be <a href="https://theconversation.com/keeping-coronavirus-vaccines-at-subzero-temperatures-during-distribution-will-be-hard-but-likely-key-to-ending-pandemic-146071">stored and shipped at ultra-low temperatures</a>. These infrastructure requirements make whole-virus vaccines much more feasible for use in remote locations of the U.S., as well as across the world.</p>
<h2>5. What are some disadvantages of whole virus vaccines?</h2>
<p>There are some downsides to whole virus vaccines.</p>
<p>To produce inactivated virus vaccines, you must first produce a huge amount of live coronavirus and then inactivate it. There is a <a href="https://doi.org/10.1016/j.vaccine.2021.02.023">small, but legitimate biohazard risk</a> associated with producing a lot of live coronavirus. A second disadvantage is that inactivated virus and viral vector vaccines <a href="https://doi.org/10.1111/j.1469-0691.2012.03971.x">might not produce strong protection in immunocompromised patients</a>. </p>
<p>Finally, producing whole virus vaccines is much more labor intensive compared to making mRNA vaccines. You must grow, then purify and then inactivate the virus while carefully checking the quality at each step. This long production process makes it hard to produce large amounts of the vaccine. For the same reasons, redesigning or updating whole-virus vaccines for future variants is more difficult compared to <a href="https://theconversation.com/how-can-scientists-update-coronavirus-vaccines-for-omicron-a-microbiologist-answers-5-questions-about-how-moderna-and-pfizer-could-rapidly-adjust-mrna-vaccines-172943">simply changing the code of nucleic acid-based</a> or protein-based vaccine.</p>
<p>Looking at the pros and cons of each vaccine type, we believe virus-based vaccines could play an important role in generating a long-lasting, broad immunity against a rapidly mutating virus. But easily updated mRNA or protein-based approaches that can be fine-tuned to the latest variants can also be key in containing the spread of the pandemic. With vaccines of all types in the works, public health officials and governments around the world will have more tools at their disposal to deal with whatever the coronavirus brings next.</p>
<p>[<em>Get fascinating science, health and technology news.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-fascinating">Sign up for The Conversation’s weekly science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/181926/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Existing coronavirus vaccines are not as effective against newer variants of the virus. Two vaccine experts explain how new vaccines currently in development will likely offer better protection.Vaibhav Upadhyay, Postdoctoral Fellow of Pharmaceutical Science, University of Colorado Anschutz Medical CampusKrishna Mallela, Professor of Pharmaceutical Science, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1814172022-04-26T12:14:00Z2022-04-26T12:14:00ZHow Robert Langer, a pioneer in delivering mRNA into the body, failed repeatedly but kept going: ‘They said I should give up, but I don’t like to give up’<figure><img src="https://images.theconversation.com/files/458348/original/file-20220415-26-upvb6i.jpg?ixlib=rb-1.1.0&rect=0%2C16%2C5640%2C3740&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Robert Langer</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/robert-langer-of-mits-langer-labs-is-photographed-on-april-news-photo/472982424?adppopup=true">Pat Greenhouse/The Boston Globe via Getty Images</a></span></figcaption></figure><p><em>The mRNA vaccines developed against COVID-19 owe a lot to the work of Robert Langer, a pioneer in the delivery of mRNA. <a href="https://scholar.google.com/citations?user=5HX--AYAAAAJ&hl=en">Langer</a>, who is the Massachusetts Institute of Technology David H. Koch Institute Professor and director of the Langer Lab, helped lay the foundation for the underlying delivery mechanism that has led to the development of the first commercial mRNA vaccines, which can be used for a variety of infectious diseases and conditions. Langer is a co-founder of Moderna, the biotech company that developed an mRNA vaccine against COVID-19. He also has authored more than 1,500 scientific papers and is the most-cited engineer in history.</em></p>
<p><em>Langer published the first paper to show that it was possible to deliver nucleic acids like RNA and DNA to the body via tiny particles. He spoke in March 2022 at the <a href="https://www.imaginesolutionsconference.com/">2022 Imagine Solutions Conference</a> in Naples, FL. about his journey from a chemical engineering doctorate to helping develop technology for various lifesaving treatments.</em></p>
<p><em>Below are some highlights from the discussion. Answers have been edited for brevity and clarity.</em></p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/LfuY4DMtco4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Robert Langer speaks at the Imagine Solutions Conference 2022.</span></figcaption>
</figure>
<h2>How did you end up where you are in your field?</h2>
<p><strong>Robert Langer:</strong> My story is not straightforward by any means. I got my doctorate in chemical engineering from MIT in 1974. One of the things I thought about doing was education, because when I was a graduate student at MIT I helped start a school in Cambridge, The Group School. And I got very involved in developing new chemistry and math curricula. </p>
<p>And I wrote to all these colleges and none of them wrote me back, so I started to think, well, what other way could I use my science and engineering education to help people? And I thought about medicine. I wrote to a lot of hospitals and medical schools. They didn’t write back to me either.</p>
<p>And then one day one of the people at my MIT lab said, “Bob, you know, there’s a surgeon named <a href="https://www.pnas.org/doi/full/10.1073/pnas.0806582105">Judah Folkman</a> in Boston and sometimes he hires unusual people.”</p>
<h2>From 1974 to 1977 you worked as a postdoctoral fellow at the Children’s Hospital Boston and at Harvard Medical School under Folkman. How did your work with Folkman influence your career?</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/458352/original/file-20220415-24-6xc04s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A balding man with glasses wearing a lab coat over a white shirt and tie sits at a lab bench surrounded by test tubes and lab equipment." src="https://images.theconversation.com/files/458352/original/file-20220415-24-6xc04s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/458352/original/file-20220415-24-6xc04s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/458352/original/file-20220415-24-6xc04s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/458352/original/file-20220415-24-6xc04s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/458352/original/file-20220415-24-6xc04s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=508&fit=crop&dpr=1 754w, https://images.theconversation.com/files/458352/original/file-20220415-24-6xc04s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=508&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/458352/original/file-20220415-24-6xc04s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=508&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Dr. Judah Folkman (1933-2008) explored the role of blood vessels in disease and faced heavy skepticism.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/dr-judah-folkman-explored-the-role-of-blood-vessels-in-news-photo/474014739?adppopup=true">Bill Greene/The Boston Globe via Getty Images</a></span>
</figcaption>
</figure>
<p>Dr. Folkman’s idea of how tumors grew was actually quite controversial. His theory was that tumors secreted a chemical signal, which he called TAF, tumor angiogenesis factor. And that would cause blood vessels to grow to the tumor. The tumor then could spread through those blood vessels. That’s a process called metastasis, which often kills people.</p>
<p>His theory was that if you could stop blood vessels maybe that would be a new way to stop cancer. To solve this problem we had to deliver large molecules to the body through tiny particles. Nobody before us had done that, and we were told it was impossible.</p>
<p>I spent about two years working in the laboratory, and I found over 200 different ways to get this to not work. Eventually I was able to make little microspheres, or nanospheres. We published our findings in the <a href="https://www.nature.com/articles/263797a0">journal Nature</a>. This was the first time nucleic acids had ever been delivered through tiny particles for any period of time.</p>
<h2>What was the process for obtaining the patent?</h2>
<p>Folkman and I filed for a patent, but the patent examiner rejected it five years in a row. And all the people at the hospital told me I was wasting a lot of money for the hospital. They said I should give up, but I don’t like to give up.</p>
<p>When we first started doing this, everybody told me it was impossible and that it could never work. So I did what’s called a science citation search, looking back at our 1976 Nature paper. One of the papers I found was really helpful. I had no idea it was even written but I found that five of the top material scientists in the world said that Folkman and I had shown some surprising results that clearly demonstrate that this idea could work.</p>
<p>We showed that to the examiner and he said, well, that’s interesting. He said, I’ll allow the patent if you can get written affidavits from these five people that they really wrote it. So I wrote them and they wrote back and sent the affidavits. We got this really broad patent, and with that patent I got involved in starting companies. </p>
<h2>What did this process teach you?</h2>
<p>I learned that if you’re not your own champion, nobody else will be. So I got involved in patenting things, and my students were very interested in seeing their work make a difference. That’s what led to a number of different companies, some of which we started and others which we guided, developing many products used today. My story is sort of one person’s example of how you can try to use science to help relieve suffering and prolong life.</p>
<p>[<em>Over 150,000 readers rely on The Conversation’s newsletters to understand the world.</em> <a href="https://memberservices.theconversation.com/newsletters/?source=inline-150ksignup">Sign up today</a>.]</p><img src="https://counter.theconversation.com/content/181417/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Robert Langer co-founded Moderna. For a list of entities with which R.L. is, or has been recently involved, compensated or uncompensated, see:
<a href="https://www.dropbox.com/s/yc3xqb5s8s94v7x/Rev%20Langer%20COI.pdf?dl=0">https://www.dropbox.com/s/yc3xqb5s8s94v7x/Rev%20Langer%20COI.pdf?dl=0</a>
</span></em></p>Moderna co-founder Robert Langer developed the process that made COVID-19 vaccines possible. He spoke about his journey helping develop the science for various lifesaving treatments.Robert Langer, Institute Professor, Massachusetts Institute of Technology (MIT)Licensed as Creative Commons – attribution, no derivatives.