tag:theconversation.com,2011:/us/topics/immune-31420/articlesImmune – The Conversation2020-05-08T12:21:15Ztag:theconversation.com,2011:article/1368162020-05-08T12:21:15Z2020-05-08T12:21:15ZWhat needs to go right to get a coronavirus vaccine in 12-18 months<figure><img src="https://images.theconversation.com/files/333429/original/file-20200507-49556-zcna08.jpg?ixlib=rb-1.1.0&rect=0%2C22%2C7238%2C4616&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A coronavirus vaccine is coming, but when?</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/syringes-and-injectable-medications-royalty-free-image/1161382041?adppopup=true"> Francesco Carta fotografo/Moment via Getty Images</a></span></figcaption></figure><p>I, like many Americans, miss the pre-pandemic world of hugging family and friends, going to work and having dinner at a restaurant. A protective vaccine for SARS-Cov2 is likely to be <a href="https://doi.org/10.1002/emmm.201403876">the most effective public health tool</a> to get back to that world. </p>
<p>Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, cautiously estimates that a vaccine could be available in <a href="https://www.npr.org/sections/coronavirus-live-updates/2020/04/30/848478507/fauci-says-its-doable-to-have-millions-of-doses-of-covid-19-vaccine-by-january">12 to 18 months</a>. </p>
<p>I am a <a href="https://scholar.google.com/citations?user=-pDNdhcAAAAJ&hl=en&oi=sra">professor of microbiology and immunology</a> and study how the immune system develops. I think Dr. Fauci’s estimate is an optimistic one, but possible. </p>
<p>Traditional vaccine development is a long and complicated process. Only about 6% of vaccine candidates are eventually <a href="https://doi.org/10.1371/journal.pone.0057755">approved for public use</a>, and the process takes <a href="https://doi.org/10.1371/journal.pone.0057755">10.7 years, on average</a>.</p>
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<span class="caption">Anthony Fauci is estimating a coronavirus vaccine will be developed faster than any other vaccine in history.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Virus-Outbreak-Trump/711244f1bb2e4e219041e8f99dc7b552/247/0">AP Photo/Patrick Semansky</a></span>
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<p>But these are not traditional times. Researchers around the world are <a href="https://doi.org/10.1038/d41573-020-00073-5">innovating the process of vaccine development</a> in real time to develop a vaccine as fast as possible. So how close are we to a vaccine?</p>
<h2>A step-by-step process</h2>
<p>Vaccines prevent disease by boosting a person’s natural immune response against a microbe that they have <a href="https://www.cdc.gov/vaccines/vpd/vpd-vac-basics.html">not encountered before</a>. There are a number of different types of vaccines in development for SARS-CoV-2 and they fall into three broad categories: <a href="https://theconversation.com/labs-are-experimenting-with-new-but-unproven-methods-to-create-a-coronavirus-vaccine-fast-134319">traditional killed-virus vaccines, protein-based vaccines and gene-based vaccines</a>. No matter the type, every single vaccine candidate must go through the same vetting process before it can be put into use. </p>
<p>Once researchers have developed a potential candidate, they begin the first step of testing in laboratories, called preclinical studies. Scientists use laboratory animals to examine if the candidate vaccine induces an immune response to the virus and to check whether the vaccine causes any obvious medical problems. </p>
<p>Once a vaccine is proven safe in animals, researchers begin human testing. This is where the <a href="https://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/BiologicsLicenseApplicationsBLAProcess/ucm133096.htm">federal Food and Drug Administration</a> begins to regulate the process. </p>
<p>Phase 1 studies test for safety and proof-of-concept. Researchers give a small number of human volunteers the vaccine. Then they look for medical problems and see if it induces some sort of immune response.</p>
<p>In Phase 2 studies, researchers give the vaccine to hundreds of volunteers to determine the optimal vaccine composition, dose and vaccination schedule.</p>
<p>The final step before a vaccine is approved by the FDA for broad use is a Phase 3 trial. These involve <a href="https://doi.org/10.1191%2F0962280204sm356ra">thousands of volunteers</a> and provide data on how good the vaccine is at preventing infection. These large trials will also uncover rarer side effects or health issues that may not show up in the smaller trials. </p>
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<a href="https://images.theconversation.com/files/333435/original/file-20200507-49569-11xpm4z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/333435/original/file-20200507-49569-11xpm4z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/333435/original/file-20200507-49569-11xpm4z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/333435/original/file-20200507-49569-11xpm4z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/333435/original/file-20200507-49569-11xpm4z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/333435/original/file-20200507-49569-11xpm4z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/333435/original/file-20200507-49569-11xpm4z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/333435/original/file-20200507-49569-11xpm4z.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>
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<span class="caption">Some side effects are rare, so testing must be thorough before a vaccine is approved.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/doctor-giving-patient-injection-in-volunteer-clinic-royalty-free-image/573103329?adppopup=true">Jose Luis Pelaez Inc/DigitalVision via Getty Images</a></span>
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<p>If in any of these phases a vaccine candidate appears to be ineffective or cause harm to people, the researchers must start over with a new candidate.</p>
<p>After a vaccine candidate successfully completes these clinical trials, a medical regulatory panel in the FDA looks at the evidence, and if the vaccine is effective and safe, approves it for general use. Experts estimate that the whole process costs between <a href="https://www.passporthealthusa.com/2018/02/how-much-does-it-cost-to-develop-a-new-vaccine/">US$1 billion and $5 billion</a>.</p>
<p>But approval is not the only hurdle. As has been demonstrated by the <a href="https://www.nytimes.com/2020/04/15/us/coronavirus-cases-update-live.html">severe lack of coronavirus testing</a>, easy and fast production of a test or vaccine is as critical as having one that works.</p>
<p>Both clinical efficacy and ease of production must be considered when asking how long until a vaccine is ready.</p>
<h2>Current promising candidates</h2>
<p>As of April 30, 2020, there were eight vaccine candidates currently in Phase 1 (or joint Phase 1/Phase 2) clinical trials and 94 vaccines candidates <a href="https://www.who.int/who-documents-detail/draft-landscape-of-covid-19-candidate-vaccines">in preclinical studies</a>.</p>
<p>Three of the eight are <a href="http://www.chictr.org.cn/showprojen.aspx?proj=52227">traditional vaccines</a> that use <a href="https://clinicaltrials.gov/ct2/show/NCT04352608?term=Sinovac&cntry=CN&draw=2&rank=9">inactivated</a> or killed virus. Two of the others are <a href="http://www.chictr.org.cn/showprojen.aspx?proj=51154">protein-based</a> vaccines that use a <a href="https://clinicaltrials.gov/ct2/show/NCT04324606?term=vaccine&cond=covid-19&draw=2&rank=3">modified cold virus to deliver the protein</a> that will stimulate the immune response.</p>
<p>The final three vaccines in Phase 1 or 2 trials, and the only two in the U.S., are gene-based vaccines. To me, these seem like the most promising.</p>
<p>Gene-based vaccines contain a gene or part of a gene from the virus that causes COVID-19, but not the virus itself. When a person is injected with one of these vaccines, their own cells read the injected gene and make a protein that is a part of the coronavirus. This one protein isn’t dangerous by itself, but it should trigger an immune response that would lead to immunity from the coronavirus.</p>
<p><a href="https://theconversation.com/labs-are-experimenting-with-new-but-unproven-methods-to-create-a-coronavirus-vaccine-fast-134319">Gene-based vaccines</a> come in DNA form, like the vaccine <a href="https://clinicaltrials.gov/ct2/show/NCT04336410?term=inovio&cond=covid-19&draw=2&rank=1">in Phase 1 clinical trials</a> from Inovio Pharmaceuticals in the U.S., or in RNA form, like the vaccine in a simultaneous Phase 1/Phase 2 trial from the <a href="https://www.clinicaltrialsregister.eu/ctr-search/search?query=BNT162-01">German company BioNTech</a> and the vaccine in Phase 1 trials from the <a href="https://clinicaltrials.gov/ct2/show/NCT04283461?term=vaccine&cond=covid-19&draw=2&rank=4">U.S.-based Moderna</a>.</p>
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<span class="caption">Gene-based vaccines are unproven, but offer effective protection and ease of production.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hepatitis-b-viruses-and-dna-illustration-royalty-free-illustration/758308151?adppopup=true">KATERYNA KON/SCIENCE PHOTO LIBRARY via Getty Images</a></span>
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<p>No gene-based vaccines have ever been approved for human use, but DNA vaccines are used on <a href="https://dx.doi.org/10.1038%2Fnrg2432">animals</a>, and a few were in <a href="https://doi.org/10.1056/NEJMoa1708120">clinical trials</a> for <a href="https://www.technologyreview.com/2016/08/02/158531/us-government-starts-test-of-zika-vaccine-in-humans/">the Zika virus</a>.</p>
<p>In the past, researchers have struggled to develop DNA vaccines that produce strong immune responses, but new techniques <a href="https://doi.org/10.1586/erv.11.188">look promising</a>. RNA vaccines tend <a href="https://doi.org/10.1038/nrd.2017.243">to be more effective</a> in animal studies but have also required innovations before human use. It may be that the time of <a href="https://dx.doi.org/10.1038%2Fnrg2432">gene-based vaccines has arrived</a>.</p>
<p>Another benefit of gene-based vaccines is that manufacturers would likely be able to produce large amounts <a href="https://dx.doi.org/10.3389%2Ffimmu.2019.00594">much faster than traditional vaccines</a>. DNA and RNA vaccines would also be <a href="https://dx.doi.org/10.1038%2Fnrg2432">more shelf–stable than conventional vaccines</a> since they don’t use ingredients like cell components or chicken eggs. This would make distribution, especially to rural areas, easier.</p>
<h2>Still a long road to implementation</h2>
<p>The three gene-based vaccines and the five other candidates face many challenges before you or I will be vaccinated. The fact that they are in Phase 1 and 2 trials is encouraging, but the very point of clinical trials is to reveal any problems with a vaccine candidate.</p>
<p>And there are a <a href="https://doi.org/10.1101/021543">lot of potential problems</a>. The preclinical results in laboratory animals might not translate well to people. The level of immune protection might be low. And people may react adversely when injected with the vaccine.</p>
<p>Any coronavirus vaccine could also produce a dangerous reaction called immune enhancement, where the vaccine actually worsens the symptoms of a coronavirus infection. This is rare, but <a href="https://doi.org/10.1073/pnas.2005456117">has happened with past vaccine candidates</a> for dengue fever and other viruses.</p>
<p>So, how long before we have a vaccine against the COVID-19 virus? </p>
<p>No vaccines have made it through Phase 1 or Phase 2 trials yet, and Phase 3 trials generally take between one and four years. If researchers get lucky and one of these first vaccines is both safe and effective, we are still at least a year away from knowing that. At that point manufacturers would need to start producing and distributing the vaccine at a massive scale. </p>
<p>It is unclear what percent of the population would need to be vaccinated against SARS-CoV-2, but in general, you need to immunize between 80% and 95% of the population to have effective <a href="https://doi.org/10.1093/cid/cir007">herd immunity</a>. Depending on what the virus does in the coming months, that might not be necessary, but if it is, that’s 260-300 million people in the U.S. alone.</p>
<p>Researchers are doing everything they can to develop a vaccine as fast as possible while still making sure it is effective and safe. Manufacturers can help by preparing flexible systems that could be ready to produce whichever candidate gets across the finish line first.</p>
<p>If everything goes well, Fauci’s 12- to 18-month prediction may be right. If so, it will be thanks to the tireless work of scientists, the support of international organizations and manufacturers all innovating and working together to fight this virus. </p>
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<p class="fine-print"><em><span>Marcos E. García-Ojeda receives funding from the Howard Hughes Medical Institute (HHMI) Inclusive Excellence Grant Intiative.</span></em></p>Vaccine development is usually a long process. The coronavirus pandemic is forcing researchers to innovate and test potential vaccines faster than ever before.Marcos E. García-Ojeda, Professor of Molecular and Cell Biology, University of California, MercedLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1371452020-05-05T12:20:41Z2020-05-05T12:20:41ZYour genes could determine whether the coronavirus puts you in the hospital – and we’re starting to unravel which ones matter<figure><img src="https://images.theconversation.com/files/332506/original/file-20200504-83725-1ijhd03.jpg?ixlib=rb-1.1.0&rect=286%2C0%2C8411%2C4900&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The relationship between the coronavirus and human genetics is murky. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/virus-cells-attacking-a-dna-strand-royalty-free-image/1183281148?adppopup=true">fatido/E+ via Getty Images</a></span></figcaption></figure><p><em>The Research Brief is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>When some people become infected with the coronavirus, they only develop <a href="https://theconversation.com/infected-with-the-coronavirus-but-not-showing-symptoms-a-physician-answers-5-questions-about-asymptomatic-covid-19-137029">mild or undetectable cases of COVID-19</a>. Others suffer severe symptoms, fighting to breathe on a ventilator for weeks, if they survive at all. </p>
<p>Despite a concerted global scientific effort, doctors <a href="https://fivethirtyeight.com/features/why-are-some-young-healthy-people-getting-severe-covid-19/">still lack a clear picture</a> of why this is. </p>
<p>Could genetic differences explain the differences we see in symptoms and severity of COVID-19?</p>
<p>To test this, we used computer models to analyze known genetic variation within the human immune system. The <a href="https://dx.doi.org/10.1128/JVI.00510-20">results of our modeling</a> suggest that there are in fact differences in people’s DNA that could influence their ability to respond to a SARS-CoV-2 infection.</p>
<h2>What we did</h2>
<p>When a virus infects human cells, the body reacts by turning on what are essentially anti-virus alarm systems. These alarms identify viral invaders and tell the immune system to send cytotoxic T cells – a type of white blood cell – to destroy the infected cells and hopefully slow the infection.</p>
<p>But not all alarm systems are created equal. People have different versions of the same genes – called alleles – and some of these alleles are more <a href="https://dx.doi.org/10.1128%2FCMR.00048-08">sensitive to certain viruses or pathogens than others</a>. </p>
<p>To test whether different alleles of this alarm system could explain some of the range in immune responses to SARS-CoV-2, we first retrieved a list of all the proteins that make up the coronavirus from an <a href="https://www.ncbi.nlm.nih.gov/refseq/">online database</a>.</p>
<p>We then took that list and used existing computer algorithms to predict how well different versions of the anti-viral alarm system detected these coronavirus proteins. </p>
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<a href="https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=802&fit=crop&dpr=1 600w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=802&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=802&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1008&fit=crop&dpr=1 754w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1008&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/332509/original/file-20200504-83745-1qdcr8d.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1008&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">A model of an HLA protein (green and yellow) bound to a piece of a virus (orange and blue) – in this case, influenza.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/HLA-B27#/media/File:HLA-B*2705-peptide_in_complex_with_influenza_nucleoprotein_NP383-391.png">Prot reimage via Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<h2>Why it matters</h2>
<p>The part of the alarm system that we tested is called the human leukocyte antigen system, or HLA. Each person has multiple alleles of the genes that make up their HLA type. Each allele codes for a different HLA protein. These proteins are the sensors of the alarm system and find intruders by binding to various peptides – chains of amino acids that make up parts of the coronavirus – that are foreign to the body.</p>
<p>Once an HLA protein binds to a virus or piece of a virus, it transports the intruder to the cell surface. This “marks” the cell as infected and from there the immune system will kill the cell.</p>
<p>In general, the more peptides of a virus that a person’s HLAs can detect, the <a href="https://dx.doi.org/10.4049%2Fjimmunol.1302101">stronger the immune response</a>. Think of it like a more sensitive sensor of the alarm system. </p>
<p>The results of our modeling predict that some HLA types bind to a large number of the SARS-CoV-2 peptides while others bind to very few. That is to say, some sensors may be better tailored to SARS-CoV-2 than others. If true, the specific HLA alleles a person has would likely be a factor in how effective their immune response is to COVID-19. </p>
<p>Because our study only used a computer model to make these predictions, we decided to test the results using clinical information from the 2002-2004 SARS outbreak.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1216&fit=crop&dpr=1 600w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1216&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1216&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/332520/original/file-20200504-83769-qfcp35.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The section of DNA that codes for HLAs is on the sixth chromosome.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HLA_MHC_Complex_illustration.jpg">Pdeitiker at English Wikipedia / Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We found similarities in how effective alleles were at identifying SARS and SARS-CoV-2. If an HLA allele appeared to be bad at recognizing SARS-CoV-2, it was also bad at recognizing SARS. Our analysis predicted that one allele, called B46:01, is particularly bad with regards to both SARS-CoV-2 and SARS-CoV. Sure enough, previous studies showed that people with this allele tended to have more <a href="https://doi.org/10.1186/1471-2350-4-9">severe SARS infections</a> and higher viral loads than people with other versions of the HLA gene. </p>
<h2>What’s next?</h2>
<p>Based on our study, we think variation in HLA genes is part of the explanation for the huge differences in infection severity in many COVID-19 patients. These differences in the HLA genes are probably not the only genetic factor that affects severity of COVID-19, but they may be a significant piece of the puzzle. It is important to further study how HLA types can clinically affect COVID-19 severity and to test these predictions using real cases. Understanding how variation in HLA types may affect the clinical course of COVID-19 could help identify individuals at higher risk from the disease.</p>
<p>To the best of our knowledge, this is the first study to evaluate the relationship between viral proteins across a wide range of HLA alleles. Currently, we know very little about the relationship between many other viruses and HLA type. In theory, we could repeat this analysis to better understand the genetic risks of many viruses that currently or could potentially infect humans.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p><img src="https://counter.theconversation.com/content/137145/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Reid Thompson receives funding from the Department of Veterans Affairs, and the Sunlin and Priscilla Chou Foundation. </span></em></p><p class="fine-print"><em><span>Abhinav Nellore and Austin Nguyen 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>Researchers from Oregon Health and Science University found that variations in genes that code for parts of the cellular alarm system might play a role in how well people fight off COVID-19.Austin Nguyen, PhD Candidate in Computational Biology and Biomedical Engineering, Oregon Health & Science UniversityAbhinav Nellore, Assistant Professor of Biomedical Engineering & Surgery, Oregon Health & Science UniversityReid Thompson, Assistant Professor of Radiation Medicine, Oregon Health & Science UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1348832020-04-07T12:10:54Z2020-04-07T12:10:54ZWhat does ‘recovered from coronavirus’ mean? 4 questions answered about how some survive and what happens next<figure><img src="https://images.theconversation.com/files/325779/original/file-20200406-51213-cwvlgt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Recovery is the result for most coronavirus patients</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Virus-Outbreak-Ohio/1cb343e672ce4d76a1451d15b067c2c6/22/0">AP Photo/Tony Dejak</a></span></figcaption></figure><p>The coronavirus is certainly scary, but despite the constant reporting on total cases and a climbing death toll, the reality is that the vast majority of people who come down with COVID-19 survive it. Just as the number of cases grows, so does another number: those who have recovered.</p>
<p>In mid-March, the number of patients in the U.S. who had officially recovered from the virus was close to zero. That number is now <a href="https://coronavirus.jhu.edu/map.html">in the tens of thousands</a> and is climbing every day. But recovering from COVID-19 is more complicated than simply feeling better. Recovery involves biology, epidemiology and a little bit of bureaucracy too. </p>
<h2>How does your body fight off COVID-19?</h2>
<p>Once a person is exposed the coronavirus, the body starts producing <a href="https://www.mblintl.com/products/what-are-antibodies-mbli/">proteins called antibodies to fight the infection</a>. As these <a href="https://www.statnews.com/2020/03/27/serological-tests-reveal-immune-coronavirus/">antibodies start to successfully contain the virus</a> and keep it from replicating in the body, symptoms usually begin to lessen and you start to feel better. Eventually, if all goes well, your immune system will completely destroy all of the virus in your system. A person who was infected with and survived a virus with no long-term health effects or disabilities has “recovered.”</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/325790/original/file-20200406-96913-9v6z5k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/325790/original/file-20200406-96913-9v6z5k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/325790/original/file-20200406-96913-9v6z5k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=524&fit=crop&dpr=1 600w, https://images.theconversation.com/files/325790/original/file-20200406-96913-9v6z5k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=524&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/325790/original/file-20200406-96913-9v6z5k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=524&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/325790/original/file-20200406-96913-9v6z5k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=658&fit=crop&dpr=1 754w, https://images.theconversation.com/files/325790/original/file-20200406-96913-9v6z5k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=658&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/325790/original/file-20200406-96913-9v6z5k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=658&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Your immune system finds and destroys viruses in the body, and will remember invaders it has seen before.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/cell-binding-antigen-illustration-royalty-free-illustration/1148113635?adppopup=true">Keith Chambers/Science Photo Library via Getty Images</a></span>
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<p>On average, a person who is infected with SARS-CoV-2 will feel ill for about seven days from the onset of symptoms. Even after symptoms disappear, there still may be small amounts of the virus in a patient’s system, and they should stay <a href="https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/steps-when-sick.html">isolated for an additional three days</a> to ensure they have truly <a href="https://health.usnews.com/conditions/articles/coronavirus-recovery-what-to-know">recovered and are no longer infectious</a>. </p>
<h2>What about immunity?</h2>
<p>In general, once you have recovered from a viral infection, your body will keep cells called lymphocytes in your system. These cells “remember” viruses they’ve previously seen and can react quickly to fight them off again. If you are exposed to a virus you have already had, your antibodies will likely stop the virus before it starts causing symptoms. <a href="https://dx.doi.org/10.5114%2Fceji.2018.77390">You become immune</a>. This is the <a href="https://www.ncbi.nlm.nih.gov/books/NBK27158/">principle behind many vaccines</a>.</p>
<p>Unfortunately, immunity isn’t perfect. For many viruses, like mumps, immunity can wane over time, leaving you <a href="https://www.sciencedaily.com/releases/2016/04/160421145747.htm">susceptible to the virus in the future</a>. This is why you need to get revaccinated – those “booster shots” – occasionally: to prompt your immune system to make more antibodies and memory cells. </p>
<p>Since this coronavirus is so new, scientists still don’t know whether people who recover from COVID-19 are <a href="https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html">immune to future infections of the virus</a>. Doctors are finding antibodies in ill and recovered patients, and <a href="https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html">that indicates the development of immunity</a>. But the question remains how long that immunity will last. Other coronaviruses like <a href="https://doi.org/10.1002/jmv.25685">SARS and MERS produce an immune response</a> that will protect a person at least for a short time. I would suspect the same is true of SARS-CoV-2, but the research simply hasn’t been done yet to say so definitively. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/325807/original/file-20200406-125671-10joxso.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/325807/original/file-20200406-125671-10joxso.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/325807/original/file-20200406-125671-10joxso.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/325807/original/file-20200406-125671-10joxso.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/325807/original/file-20200406-125671-10joxso.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/325807/original/file-20200406-125671-10joxso.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/325807/original/file-20200406-125671-10joxso.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/325807/original/file-20200406-125671-10joxso.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">A coronavirus test kit. Necessary before a person can be declared officially recovered.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Virus-Outbreak-Texas/44d66d83f9954836916e156ffca0c03e/9/0">AP Photo/David J. Phillip</a></span>
</figcaption>
</figure>
<h2>Why have so few people officially recovered in the US?</h2>
<p>This is a dangerous virus, so the Centers for Disease Control and Prevention is being extremely careful when deciding what it means to recover from COVID-19. Both medical and testing criteria must be met before a person is <a href="https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html">officially declared recovered</a>.</p>
<p>Medically, a person must be fever-free without fever-reducing medications for three consecutive days. They must show an improvement in their other symptoms, including reduced coughing and shortness of breath. And it must be at least seven full days <a href="https://health.usnews.com/conditions/articles/coronavirus-recovery-what-to-know">since the symptoms began</a>. </p>
<p>In addition to those requirements, the CDC guidelines say that a person must test negative for the coronavirus twice, with the <a href="https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/care-for-someone.html">tests taken at least 24 hours apart</a>. </p>
<p>Only then, if both the symptom and testing conditions are met, is a person officially considered recovered by the CDC.</p>
<p>This second testing requirement is likely why there were so few official recovered cases in the U.S. until late March. Initially, there was a <a href="https://www.nytimes.com/2020/03/18/health/coronavirus-test-shortages-face-masks-swabs.html">massive shortage of testing in the U.S.</a> So while many people were certainly recovering over the last few weeks, this could not be officially confirmed. As the country enters the height of the pandemic in the coming weeks, focus is still on <a href="https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html">testing those who are infected</a>, not those who have likely recovered. </p>
<p>Many more people are being tested now that states and private companies have begun <a href="https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/testing-in-us.html">producing and distributing tests</a>. As <a href="https://www.dispatch.com/news/20200406/coronavirus-in-ohio-from-its-rocky-start-testing-for-covid-19-slowly-ramping-up">the number of available tests increases</a> and the pandemic eventually slows in the country, more testing will be available for those who have appeared to recover. As people who have already recovered are tested, the appearance of any new infections will help researchers learn <a href="https://www.statnews.com/2020/03/24/we-need-smart-coronavirus-testing-not-just-more-testing/">how long immunity can be expected to last</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/325803/original/file-20200406-103690-4fgjlt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/325803/original/file-20200406-103690-4fgjlt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/325803/original/file-20200406-103690-4fgjlt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/325803/original/file-20200406-103690-4fgjlt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/325803/original/file-20200406-103690-4fgjlt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/325803/original/file-20200406-103690-4fgjlt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/325803/original/file-20200406-103690-4fgjlt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/325803/original/file-20200406-103690-4fgjlt.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">Drive-by testing stations are opening across the U.S. as tests become more available.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Virus-Outbreak-Texas/8752667731464e1588f2cc16279e6428/20/0">AP Photo/David J. Phillip</a></span>
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</figure>
<h2>Once a person has recovered, what can they do?</h2>
<p>Knowing whether or not people are immune to COVID-19 after they recover is going to determine what individuals, communities and society at large can do going forward. If scientists can show that recovered patients are immune to the coronavirus, then a person who has recovered could in theory <a href="https://www.vox.com/2020/3/30/21186822/immunity-to-covid-19-test-coronavirus-rt-pcr-antibody">help support the health care system</a> by caring for those who are infected. </p>
<p>Once communities pass the peak of the epidemic, the number of new infections will decline, while the number of <a href="https://www.newsweek.com/china-says-passed-peak-coronavirus-epidemic-covid-19-1491863">recovered people will increase</a>. As these trends continue, the risk of transmission will fall. Once the risk of transmission has fallen enough, community-level isolation and social distancing orders will begin to relax and businesses will start to reopen. Based on what other countries have gone through, it will be <a href="https://www.nature.com/articles/d41586-020-00154-w">months until the risk of transmission is low</a> in the U.S.</p>
<p>But before any of this can happen, the U.S. and the world need to make it through the peak of this pandemic. Social distancing works to slow the spread of infectious diseases and <a href="https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/what-you-can-do.html">is working for COVID-19</a>. Many people will <a href="https://www.yalemedicine.org/stories/2019-novel-coronavirus/">need medical help to recover</a>, and social distancing will slow this virus down and give people the best chance to do so.</p>
<p>[<em>You need to understand the coronavirus pandemic, and we can help.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=upper-coronavirus-help">Read The Conversation’s newsletter</a>.]</p><img src="https://counter.theconversation.com/content/134883/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tom Duszynski does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Officially, not that many people have recovered from the coronavirus. An epidemiologist explains what has to happen for a COVID-19 survivor to get a clean bill of health.Tom Duszynski, Director Epidemiology Education, IUPUILicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1286962020-02-10T05:01:54Z2020-02-10T05:01:54ZWhat is autoinflammatory disease, the rare immune condition with waves of fever?<figure><img src="https://images.theconversation.com/files/313866/original/file-20200206-149802-8eqdou.jpg?ixlib=rb-1.1.0&rect=0%2C8%2C1000%2C657&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/pediatrician-taking-temperature-professional-thermometer-229346311">from www.shutterstock.com</a></span></figcaption></figure><p>Just over 20 years ago, people from three generations of an American family were referred to the <a href="https://www.nih.gov/">National Institutes of Health</a> (NIH) in Washington DC with an unknown disease. </p>
<p>They were ten to 82 years old and had symptoms including monthly episodes of unexplained high fevers (up to 41°C), lasting two to seven days. </p>
<p>They also had painful swollen <a href="https://www.healthdirect.gov.au/lymph-nodes">lymph nodes</a>, enlarged <a href="https://www.health.qld.gov.au/news-events/news/facts-about-your-spleen-splenectomy-immune-system-what-is">spleens</a> and livers, abdominal pain, mouth ulcers, joint pain, and a patchwork of other symptoms.</p>
<p>The symptoms, which they’d had since shortly after birth, seemed like an inflammatory reaction. However, doctors could not trace the episodes to an infection.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-inflammation-and-how-does-it-cause-disease-84997">Explainer: what is inflammation and how does it cause disease?</a>
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<p>We now know these symptoms are typical of <a href="https://www.wehi.edu.au/research-diseases/immune-health-and-infection/autoinflammatory-diseases">autoinflammatory diseases</a> – rare conditions with seemingly unprovoked episodes of fever and inflammation. </p>
<p>Because the inflammatory episodes occur regularly, the diseases are also known as “<a href="https://my.clevelandclinic.org/health/articles/17354-periodic-fever-syndrome">periodic fever syndromes</a>”. In addition to being painful and debilitating, some of the conditions can damage vital organs, such as the heart and lungs.</p>
<h2>What causes autoinflammatory disease?</h2>
<p>Autoinflammatory diseases are <a href="https://www.ncbi.nlm.nih.gov/pubmed/24247370">caused by</a> abnormal activation of the <a href="https://www.ncbi.nlm.nih.gov/books/NBK26846/">innate immune system</a>, the body’s first-line defence against invading pathogens.</p>
<p>The innate immune system is a hard-wired response that can quickly mobilise to fight foreign invaders. Among its many roles is the release of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785020/">cytokines</a>. </p>
<p>These are immune messengers critical for alerting and recruiting other cells to the fight, increasing blood circulation and inducing fever. More about cytokines later.</p>
<p>However, in autoinflammatory diseases, invading microbes don’t cause the fever and inflammation. Instead, genetic changes (mutations) lead to the innate immune system being activated for what appears to be no reason, causing uncontrolled inflammation.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-the-immune-system-19240">Explainer: what is the immune system?</a>
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<p>Autoinflammatory diseases typically begin in childhood, often from birth, and are lifelong conditions. The genetic mutations can be passed from parents to their children, leading to multiple cases of disease in an extended family. </p>
<p>Autoinflammatory diseases are different from autoimmune diseases, such as <a href="https://theconversation.com/explainer-multiple-sclerosis-32662">multiple sclerosis</a>, which are caused by defects in the adaptive immune system, a different arm of the immune response.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-are-autoimmune-diseases-22577">Explainer: what are autoimmune diseases?</a>
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<p>There are a number of different autoinflammatory diseases, often caused by different genetic mutations.</p>
<h2>How do we treat autoinflammatory disease?</h2>
<p>Autoinflammatory diseases cannot be cured, and treatment is usually to relieve symptoms during an attack. Patients are often treated with high doses of <a href="https://www.nhsinform.scot/tests-and-treatments/medicines-and-medical-aids/types-of-medicine/corticosteroids">corticosteroids</a>, a broad-brush approach to suppress the immune system.</p>
<p>Autoinflammatory diseases are also <a href="https://ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome#statistics">quite rare</a>, which in the past has made it difficult to develop specific treatments.</p>
<p>Because autoinflammatory diseases are typically associated with excess production of cytokines, they are sometimes treated with so-called biologics – antibodies that mop up these excess cytokines.</p>
<p>These are usually antibodies to the cytokines <a href="https://www.medicalnewstoday.com/articles/324841.php">tumour necrosis factor</a> (TNF) or <a href="https://www.rndsystems.com/resources/articles/interleukin-1">interleukin-1</a>. </p>
<p>However biologics are expensive, and can have <a href="https://jamanetwork.com/journals/jama/article-abstract/202873">significant</a> <a href="https://www.nature.com/articles/s41467-017-02466-4">side-effects</a>.</p>
<p>Without knowing the cause of an inflammatory disease, treatment is a trial and error process; a drug that works for one person may not work for another.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/313868/original/file-20200206-149747-11f116p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/313868/original/file-20200206-149747-11f116p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313868/original/file-20200206-149747-11f116p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=541&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313868/original/file-20200206-149747-11f116p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=541&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313868/original/file-20200206-149747-11f116p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=541&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313868/original/file-20200206-149747-11f116p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=679&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313868/original/file-20200206-149747-11f116p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=679&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313868/original/file-20200206-149747-11f116p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=679&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Antibodies against the molecule TNF (above) can be used to treat excess inflammation.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/tumor-necrosis-factor-alpha-tnf-cytokine-1246006945">from www.shutterstock.com/StudioMolekuul</a></span>
</figcaption>
</figure>
<h2>Can genetic testing help?</h2>
<p>The discovery of mutations in genes causing autoinflammatory diseases has led to the development of genetic tests to help diagnosis.</p>
<p>However, some people with autoinflammatory disease do not have a change in one of the known disease-causing genes. </p>
<p>So our researchers have established the <a href="https://www.aadry.org/">Australian Autoinflammatory Disease Registry</a> to help identify other genetic causes of autoinflammatory diseases. </p>
<h2>How we found out about the underlying mechanism</h2>
<p>While the NIH researchers were looking for a cause of the American family’s disease, another strand of the story was playing out in Australia.</p>
<p>We were looking at the role of the master cytokine TNF, which controls many aspects of the body’s inflammatory response, and its partner RIPK1.</p>
<p>Usually, the body has many checks and balances to ensure these molecules are tightly controlled. </p>
<p>But we worked with the <a href="https://www.nature.com/articles/s41586-019-1828-5_">US scientists who found</a> a critical mutation in the gene coding for RIPK1. We found this mutation, leading to changes in just one amino acid, was enough to supercharge its partner TNF into an elite killer. </p>
<p>This is what triggered the uncontrolled inflammation behind the American family’s disease.</p>
<p>Our team named this condition <a href="https://pursuit.unimelb.edu.au/articles/the-genetic-mutation-behind-a-new-autoinflammatory-disease">CRIA syndrome</a> (cleavage-resistant RIPK1-induced autoinflammatory syndrome).</p>
<h2>So what does this mean?</h2>
<p>Understanding the molecular mechanism by which CRIA syndrome causes inflammation gives us an opportunity to get to the root of the problem, and to offer an alternative to existing treatments.</p>
<p>For this American family, treatment with an agent that inhibits the faulty RIPK1 might be a tailored option.</p>
<p>Lastly, the discovery of CRIA syndrome now confirms RIPK1 can play an important role in regulating inflammation in humans. So it <a href="https://www.nature.com/articles/ni.3206">may also play</a> a role in far more common human illnesses, such as colitis (inflammation of the colon), rheumatoid arthritis and the skin condition psoriasis.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-rheumatoid-arthritis-the-condition-tennis-champion-caroline-wozniacki-lives-with-119537">What is rheumatoid arthritis, the condition tennis champion Caroline Wozniacki lives with?</a>
</strong>
</em>
</p>
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<img src="https://counter.theconversation.com/content/128696/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Silke consults for Anaxis, an Australian company developing drugs to inhibit inflammatory diseases. He has a fellowship from the NHMRC and the work on RIPK1 cleavage was also funded by the NHMRC (Project #1163581).</span></em></p><p class="fine-print"><em><span>Najoua Lalaoui receives funding from the Cancer Australia and Cure Cancer Australia Foundation (Project grant 1145588) and the Victorian Cancer Agency Mid-career Fellowship 17030. </span></em></p>A rare type of inflammatory disease that causes repeated bouts of high temperatures can run in families. Here’s what we know so far.John Silke, Leader, Infection, Inflammation and Immunity theme, Walter and Eliza Hall InstituteNajoua Lalaoui, Postdoctoral research fellow, Inflammation Division, Walter and Eliza Hall InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/952562018-05-01T15:23:42Z2018-05-01T15:23:42ZFive amazing ways redesigning biological cells could help us fight cancer<figure><img src="https://images.theconversation.com/files/216842/original/file-20180430-135806-mgzauj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cancer is the leading cause of death in the world</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/26184671492">Julio C. Valencia, NCI Center for Cancer Research</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Cancer is the <a href="http://www.who.int/cancer/resources/keyfacts/en/">leading cause of death</a> in the world. It occurs when mutations in our cells lead to unchecked growth. But what if we could engineer biological cells to fight back?</p>
<p>Synthetic biology is a rapidly developing discipline that allows us to encode new computational capabilities into DNA. In the same way that electronic circuits are made from components such as resistors and diodes with well defined functions, synthetic biologists make use of an ever growing library of genetic parts with functions such as switches and sensors. Using this toolkit, cells can be reprogrammed to detect and destroy tumours.</p>
<p>Here are five remarkable ways that synthetic biology could help us treat cancer in the future.</p>
<h2>1. A tattoo for all cancers</h2>
<p>Solid tumours within the body are often not detected until they are significantly developed. Increased calcium in blood is a signature of many cancers. Focusing on this, a group at Eidgenössische Technische Hochschule (ETH) Zurich <a href="http://stm.sciencemag.org/content/10/437/eaap8562.full">have engineered cells</a> to detect elevated levels of calcium in blood. Implanted under your skin, these engineered cells will respond to increased calcium levels by secreting melanin that cause the skin to darken. The hope is that these cells will temporarily tattoo the body, indicating that there is a potential problem needing further investigation. </p>
<h2>2. Don’t miss the target</h2>
<p>Once cancer has been detected, killing cancerous cells while sparing healthy ones is the next challenge. Researchers have built biological systems which mimic the behaviour of electronic logic circuits. DNA sequences can be designed that only produce a desired output when all of the necessary inputs are present. </p>
<p><a href="http://science.sciencemag.org/content/333/6047/1307">In this case</a>, one such “genetic logic circuit” has been developed to sense several <a href="http://www.exiqon.com/what-are-microRNAs">microRNAs</a> produced by cancerous growth, and thereby distinguish between healthy and tumour cells. Only when all of the microRNAs are present will the circuit produce the output, a single protein that causes the cancer cell to self-destruct. By detecting several signals, the chances of misclassification are reduced. </p>
<p>This treatment can be delivered by standard gene therapy techniques such as <a href="https://ghr.nlm.nih.gov/primer/therapy/procedures">engineered viruses</a>, which will spread through the body and “infect” cells with the genetic logic circuit.</p>
<h2>3. Rebooting the immune system</h2>
<p>Cancer cells have the dangerous ability to evade our immune systems. Given this, one approach to treat cancer is immunotherapy, which aims to stimulate the immune system to attack cancer cells. A group at Massachusetts Institute of Technology (MIT) recently engineered a gene circuit that <a href="https://www.cell.com/cell/abstract/S0092-8674(17)31143-1">identifies ovarian cancer cells</a>. In this case, once cancer cells are identified, the circuit essentially paints a biological bullseye on them, directing the immune system to destroy the cancer. The advantages of this approach over existing immunotherapies is that a greater number of markers can be tested and more specific therapies achieved.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/216840/original/file-20180430-135851-53as4f.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/216840/original/file-20180430-135851-53as4f.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/216840/original/file-20180430-135851-53as4f.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/216840/original/file-20180430-135851-53as4f.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/216840/original/file-20180430-135851-53as4f.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/216840/original/file-20180430-135851-53as4f.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/216840/original/file-20180430-135851-53as4f.png?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">Immune system T-cells surround a cancerous cell.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/20673870162">Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths, National Institutes of Health</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>4. Reprogrammed microbes</h2>
<p>Some types of bacteria, such as <em>Salmonella</em>, can live happily inside the tumour environment. These microbes can be engineered to detect and destroy tumours. <a href="http://stm.sciencemag.org/content/7/289/289ra84">One study</a>, led by teams in San Diego and MIT, turned a probiotic strain of bacteria into a biosensor that could detect cancers in the liver and subsequently be detected in the urine with a simple colour change test. This type of system could in principle provide a non-invasive early warning screen for tumour developments. <a href="https://www.nature.com/articles/nature18930">In another study</a> by the same groups, weakened <em>Salmonella</em> strains were engineered to release an anti-tumour toxin into the tumour environment. The uniqueness of this system over previous approaches was that the gene circuit within the bacteria produced cycles of drug delivery, thus allowing larger therapeutic doses over a longer time period. </p>
<h2>5. Broccoli has never tasted so good</h2>
<p>We all know that eating greens is good for us, but engineered bacteria can make them even healthier. A group from National University Singapore (NUS) engineered a common probiotic bacteria to stick to colorectal cancer cells and <a href="https://www.nature.com/articles/s41551-017-0181-y">convert a chemical in cruciferous vegetables</a>, such as broccoli, into a strong anti-tumour agent. They demonstrated successful conversion of food intake into the drug and a significant reduction in tumour size using their treatment. Such an approach could be used as a preventative measure to stop tumours forming and also after surgery to clean up any remaining tumour cells.</p>
<h2>Future challenges and goals</h2>
<p>So far, the majority of these approaches have been tested using simplified tumour models in mice. So, care must be taken when extrapolating to human treatments. But as a first step they have undoubtedly shown great promise. Big challenges, particularly in the case of engineered microbes, are containment - ensuring <a href="https://www.nature.com/news/gm-microbes-created-that-can-t-escape-the-lab-1.16758">engineered microbes don’t survive in the natural environment</a> - and dealing with evolutionary pressures, which render the microbes ineffective. It is now clear that these challenges are not insurmountable and clinical trials of engineered bacterial therapies <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.28365">are already proceeding</a>. </p>
<p>Synthetic biology will enable ever more sophisticated ways to treat cancer. These, combined with the knowledge generated from understanding how tumours evolve, provide hope that a significant reduction in cancer deaths can be achieved in the not too distant future.</p><img src="https://counter.theconversation.com/content/95256/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chris Barnes receives funding from The Wellcome Trust, ERC, Royal Society, Microsoft Research</span></em></p><p class="fine-print"><em><span>Alex J H Fedorec receives funding from EPSRC. </span></em></p>Synthetic biology allows us to engineer biological cells. This could help us tackle cancer in remarkable ways.Chris Barnes, Reader in Systems and Synthetic Biology, UCLAlex J H Fedorec, PhD Candidate in Synthetic Biology, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/825032017-09-27T00:02:26Z2017-09-27T00:02:26ZCurious Kids: How do we get allergic to food?<figure><img src="https://images.theconversation.com/files/182045/original/file-20170815-27094-goqd4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Allergies may be in the genes that are passed down from parents to children.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/usdagov/15031804271/in/photolist-oUiVHa-bBmd4y-6KfTaw-Ge34DY-8q6knQ-Pu1et-6ufawu-bxDJtC-4LnJex-28eWU-fJAN8D-fJUhu7-ejyQxV-bPBF4v-HdPY1-mNsyWB-5ctXoY-9H636F-mNup2y-mNsWVM-q5EEgr-amro9L-mNsRcn-7Ja7F9-mNtscz-9y4R3F-mNv4uA-coXzoG-mNuiT7-djXwKq-mNtaoz-6aexb2-mNtDf4-mNv9mj-mCaTGZ-fBBTMn-syoW1-b9JCAV-9EGjzb-dTYLiQ-zCsUKb-8GwN7a-8rSDqt-S9cZSj-anuKGE-dSPKAt-oRYgSd-PNoBz-2cKmcb-BSnfS">Flickr/U.S. Department of Agriculture</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p><em>This is an article from <a href="https://theconversation.com/au/topics/curious-kids-36782">Curious Kids</a>, a series for children. The Conversation is asking kids to send in questions they’d like an expert to answer. All questions are welcome – serious, weird or wacky!</em> </p>
<hr>
<blockquote>
<p><strong>How do we get allergic to food? – Younus, age 9, Perth</strong></p>
</blockquote>
<hr>
<p>That’s a really interesting question, and one that many scientists and doctors are also trying to understand better.</p>
<p>It all starts with the immune system. Every person has one - a group of cells, tissues and organs in the body that helps you fight infections.</p>
<p>It does this by fighting off bugs that might make you sick when they enter your body. This is very important both in keeping you well, as well as helping you recover when you do get sick with an infection.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-how-can-a-tiny-seed-actually-grow-into-a-huge-tree-77873">Curious Kids: how can a tiny seed actually grow into a huge tree?</a>
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<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/183670/original/file-20170829-14211-1s8sa4j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/183670/original/file-20170829-14211-1s8sa4j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/183670/original/file-20170829-14211-1s8sa4j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183670/original/file-20170829-14211-1s8sa4j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183670/original/file-20170829-14211-1s8sa4j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183670/original/file-20170829-14211-1s8sa4j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183670/original/file-20170829-14211-1s8sa4j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183670/original/file-20170829-14211-1s8sa4j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Your immune system helps fight off colds and flus.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/williambrawley/4195919691/in/photolist-7oMbJX-33i8HE-fbDEBz-5TvJ6s-6pypTD-5NHghz-2KKfrg-jJdFvE-GRd7i-9R4TFp-axMv2U-4ZiEHx-uc1vc-q6XfhV-eV25Hf-5ue7CY-7D337E-62rJCG-fcLSgd-82Yb5r-3fG1uY-8BHWhG-5aBP8X-5hC9nc-8wacSd-eU6QVF-8sbfoo-4ZnTP7-6yYciH-xe5A-4r4XJv-jXHrXR-anZgkL-8C1tgU-jwiam3-buK2aw-4UvVFM-5sGMXV-7NZDG3-rtFACo-4SgboA-9VRmbi-7CuRwu-Am1si-4b1M9R-5cTqVH-zbD4h-rcqsaW-7ZQd3o-55B3T5">Flickr/William Brawley</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Allergies happen when the immune system starts overreacting to other things which would not usually make you sick. These can include dust, pollens, pets, and as you mentioned, foods. </p>
<p>For example, in someone who is not allergic to cow’s milk, the immune system doesn’t react when they drink the milk. </p>
<p>But if you <em>are</em> allergic to cow’s milk, when you drink it your immune system overreacts and can cause you to have a rash, swelling or trouble breathing. </p>
<h2>Passing down allergies</h2>
<p>If there are people in your family with allergies, such as asthma, eczema, hay fever or food allergies, then you are more likely to have allergies too. </p>
<p>This means that allergies may be in the genes that are passed down from parents to children, just like there are genes that pass down the colour of your eyes and hair.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-are-allergies-and-why-are-we-getting-more-of-them-40318">What are allergies and why are we getting more of them?</a>
</strong>
</em>
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<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/183672/original/file-20170829-1572-1jn6lhw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/183672/original/file-20170829-1572-1jn6lhw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/183672/original/file-20170829-1572-1jn6lhw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=606&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183672/original/file-20170829-1572-1jn6lhw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=606&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183672/original/file-20170829-1572-1jn6lhw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=606&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183672/original/file-20170829-1572-1jn6lhw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=762&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183672/original/file-20170829-1572-1jn6lhw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=762&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183672/original/file-20170829-1572-1jn6lhw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=762&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 foods commonly cause allergies, such as cow’s milk, egg, wheat, nuts and shellfish.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/v1ctor/19722659241/in/photolist-w3PMsZ-sGpyws-F3m9Ve-6KudRn-WgCp7G-2KKpHV-7Zz5ui-Sic5tP-UV3f2f-85Bpga-9YVW1y-gc2tQe-r5UoC-adePPh-nPBBYz-dqFKUM-UYza9Z-UovE7q-ULUQ9x-otqDMH-UJf4S5-8CzceE-9Ax1Rr-TK83qz-UJeZT3-obW2bT-d4J7o3-UovEoh-pTo6Dg-7Y17oE-q3APVB-bpdP2C-5SGJ9r-TK84qa-f39D6Q-4AVHip-o7JBbo-VutsA1-9Fnvvt-8j1sxi-6yBiqg-5SEG7m-5SNggT-5SJnWV-f7PJD-oXoKV4-bTLdkX-5SBpq8-dt4NHx-UJf3v7">Flickr/Victor</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Some foods commonly cause allergies, such as cow’s milk, egg, wheat, nuts and shellfish. </p>
<p>It may be that the age when you first try these foods can affect whether you go on to become allergic to that food, and a lot of research is happening to figure out if that is true. </p>
<p>Over the next few years, I think we will understand this question better, and hopefully be able to make food allergies less common. </p>
<hr>
<p><em>Hello, curious kids! Have you got a question you’d like an expert to answer? Ask an adult to send your question to us. You can:</em></p>
<p><em>* Email your question to curiouskids@theconversation.edu.au
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* Tell us on <a href="https://twitter.com/ConversationEDU">Twitter</a> by tagging <a href="https://twitter.com/ConversationEDU">@ConversationEDU</a> with the hashtag #curiouskids, or
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<img alt="" src="https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=376&fit=crop&dpr=1 600w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=376&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=376&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/168011/original/file-20170505-21620-huq4lj.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p class="fine-print"><em><span>Lucinda Berglund has previously received a government-funded NHMRC scholarship.
She is affiliated with the University of Sydney.</span></em></p>Younus, age 9, wants to know how people become allergic to food.Lucinda Berglund, Clinical Senior Lecturer University of Sydney, Immunologist and Immunopathologist Westmead Hospital and NSW Health Pathology, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/638042016-09-26T01:31:34Z2016-09-26T01:31:34ZWhy a Zika vaccine is a long way off<figure><img src="https://images.theconversation.com/files/138703/original/image-20160921-21691-11lt6fa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A vial of the Zika Virus Investigational DNA Vaccine from the NIH.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/28716385784/in/photolist-GKUJuZ-Di6KUu-GZE8CD-GrNTdu-GbiVox-GHBkhU-FQiMih-KKyZ2J-KsvQrA-K47iFa-JRP7UF-KkqdKy-Gtdmhs">NIH Image Gallery/Flickr </a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>Recent news articles have highlighted positive findings in <a href="http://www.nbcnews.com/storyline/zika-virus-outbreak/striking-results-early-zika-vaccine-trial-n623016">experimental Zika virus pre-clinical vaccine studies in monkeys</a> and described the start of two Zika virus <a href="https://www.nih.gov/news-events/news-releases/nih-begins-testing-investigational-zika-vaccine-humans">vaccine trials</a> <a href="https://www.statnews.com/2016/06/20/zika-vaccine-inovio/">in humans</a>.</p>
<p>These stories have spurred hopes that a Zika virus vaccine will be available to prevent this infection, and its secondary effects, such as abnormal fetal development. But, even with pre-clinical and early stage clinical trials underway, we still may not see a Zika vaccine licensed and approved for use in humans for years. </p>
<p>I am a scientist who studies how vaccines are used, and a large part of my academic and teaching interest is focused on how we use evidence to make policy and regulatory decisions about vaccines.</p>
<p>Developing a vaccine requires hitting just the right sweet spot on a number of conditions, including organism strain, vaccine type, dosage and best age to vaccinate, through pre-clinical and clinical testing, licensing and approval. This process can take a lot of time, often up to <a href="https://www.health.ny.gov/prevention/immunization/vaccine_safety/science.htm">10-15</a> <a href="http://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation">years</a>. </p>
<h2>Start by learning about the disease</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/138847/original/image-20160922-22509-vsdee2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/138847/original/image-20160922-22509-vsdee2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=677&fit=crop&dpr=1 600w, https://images.theconversation.com/files/138847/original/image-20160922-22509-vsdee2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=677&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/138847/original/image-20160922-22509-vsdee2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=677&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/138847/original/image-20160922-22509-vsdee2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=851&fit=crop&dpr=1 754w, https://images.theconversation.com/files/138847/original/image-20160922-22509-vsdee2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=851&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/138847/original/image-20160922-22509-vsdee2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=851&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Zika virus, in red, isolated from a microcephaly case in Brazil.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/27385281096/in/photolist-FJ79yb-HHWHYU-EpF3rg-FQiMih-GpSMsv-GnAk1C-KKyZ2J-LeLCD3-KsvQrA-KsLWUz-KY1s31-LmtFFy-Gtdmhs">NIH Image Gallery</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
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<p>We use vaccines to <a href="https://www.niaid.nih.gov/research/how-vaccines-work">prepare our immune system</a> for the potential exposure to a disease-causing organism. When we are exposed to the vaccine, our immune system responds by producing antibodies which attack the virus or bacteria.</p>
<p>This particular exposure is then stored in the memory of the immune system, so that if the vaccinated individual is exposed to that virus or bacteria again, these antibodies can be rapidly produced in great numbers to fight back. </p>
<p>Prior to developing and testing new vaccines, extensive surveillance is done to identify all strains of the pathogen causing disease in humans. This allows scientists to weigh the benefits and costs related to which strains should be used in the vaccine. For Zika virus there are two strains – Asian and African – and so far <a href="http://dx.doi.org/10.1016/j.celrep.2016.07.049">it appears</a> that <a href="http://news.emory.edu/stories/2016/07/mulligan_zika_single_serotype/">vaccination with one strain protects against both types</a>. </p>
<h2>Different diseases require different vaccine forms</h2>
<p>Next, scientists have to decide how to make the vaccine in such a way as to safely trigger the immune system to produce antibodies against the disease. Some vaccines, such as the one for rotavirus, which causes severe diarrhea, contain <a href="http://www.chop.edu/centers-programs/vaccine-education-center/vaccine-details/rotavirus-vaccine#.V-QcM_ArKUk">weakened versions of the virus</a> that do not cause disease to trigger the immune system. Others, like <a href="http://www.chop.edu/centers-programs/vaccine-education-center/vaccine-details/influenza-vaccine#.V-QcV_ArKUk">the flu shot</a>, use purified pieces of the virus.</p>
<p>Another kind of vaccine uses virus-like particles – an empty protein shell that looks like the actual virus to the immune system – to trigger an immune response. These types of vaccines can work in two ways. Some, such as <a href="http://www.chop.edu/centers-programs/vaccine-education-center/vaccine-details/vaccine-hepatitis-b-vaccine#.V-Qcg_ArKUk">hepatitis B vaccine</a>, use injections of the whole outer virus shell to start the immune response. Others use just a <a href="http://www.who.int/biologicals/areas/vaccines/dna/en/">small piece of DNA</a> that is the code for the outside virus coat to produce the virus-like particles in the body, but with no ability to cause infection.</p>
<p>The virus-like particle approaches are playing key roles in Zika vaccine development. There are two vaccines currently undergoing clinical trials in humans, one from the National Institutes of Health and one from Inovio Pharmaceuticals, and both use the DNA virus-like particle approach. Another company, Geovax, is developing a vaccine using the <a href="http://www.geovax.com/news-events/entry/2016/02/03/geovax-to-develop-vaccine-against-zika-virus.html">whole virus-like particle</a>.</p>
<h2>Clinical trials: Phases 1, 2 and 3</h2>
<p>Developing the vaccine concept and platform is just one step. This is followed by a rigorous set of testing to show that the vaccine is safe for use in humans and works to prevent disease. These studies involve controlled clinical trials, in which the experimental vaccine, and in later phases a placebo, are given to volunteers who are intensively monitored to evaluate their immune response and any adverse events that may occur following vaccination. These clinical trials are conducted in three phases. </p>
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<img alt="" src="https://images.theconversation.com/files/138525/original/image-20160920-12465-1oowat.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/138525/original/image-20160920-12465-1oowat.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/138525/original/image-20160920-12465-1oowat.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/138525/original/image-20160920-12465-1oowat.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/138525/original/image-20160920-12465-1oowat.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/138525/original/image-20160920-12465-1oowat.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/138525/original/image-20160920-12465-1oowat.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A healthy volunteer receives the NIAID Zika vaccine.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/28523391124/in/photolist-GKUJuZ-Di6KUu-GZE8CD-GrNTdu-GbiVox-GHBkhU-FQiMih-KKyZ2J-KsvQrA-K47iFa-JRP7UF-KkqdKy-Gtdmhs">NIH Image Gallery/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Phase 1 clinical trials are usually small – often a few dozen people. They are done to evaluate if there are any very severe side effects associated with the new vaccine and to get a preliminary sense of how the body responds to the vaccine. This is where we are at with the Zika vaccine. The NIH launched this <a href="https://www.nih.gov/news-events/news-releases/nih-begins-testing-investigational-zika-vaccine-humans">initial Zika vaccine trial</a> in August 2016, and it is expected to include about 80 people. On the heels of their first study of <a href="https://www.statnews.com/2016/06/20/zika-vaccine-inovio/">40 patients</a>, <a href="http://ir.inovio.com/news/news-releases/news-releases-details/2016/Inovio-Launches-Zika-Vaccine-Trial-in-Midst-of-Puerto-Rico-Epidemic-to-Explore-Early-Signals-of-Vaccine-Efficacy/default.aspx">Inovio is currently enrolling 160 people</a> for a second Phase 1 trial of their Zika vaccine. </p>
<p>If Phase 1 trials are completed successfully, we move on to Phase 2 trials. These are larger – often a few hundred people. In these Phase 2 trials, scientists are looking not only at safety, but at how well the new vaccine produces an immune response.</p>
<p>Finally, after Phase 1 and 2 trials are finished, scientists conduct Phase 3 trials to determine the efficacy of the vaccine in preventing disease. These trials typically contain thousands of participants, with some Phase 3 trials studying up to 70,000 people. </p>
<p>This process is more complex for vaccines like the ones for Zika, because one focus group for Zika vaccines will be pregnant women. Studies must be conducted in nonpregnant people first, and <a href="http://www.future-science.com/doi/pdf/10.4155/cli.13.132">special considerations must be taken for vaccine studies in pregnant women</a>. These considerations go beyond studying the effect of the vaccine on the recipient, to monitoring the effects on the fetus and young infant as well.</p>
<p>Just completing these trials successfully does not automatically bring a new vaccine to market. Multiple reviews by expert panels advising the Food and Drug Administration and the Centers for Disease Control and Prevention are used to determine if a vaccine should be licensed for use, and then recommended for routine use, respectively. </p>
<p>The review does not stop there. Once a vaccine is licensed and recommended for use, there is continued monitoring of how many people are taking the vaccine, how well it works in widespread use, and how safe it is. These post-licensure studies, using systems like the <a href="http://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vaers/">Vaccine Adverse Event Reporting System</a> coordinated by the CDC and FDA and the <a href="http://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/index.html">Vaccine Safety Datalink</a>, often study hundreds of thousands of people who have who have received the vaccine, and are regularly reported to regulatory bodies for review. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/138704/original/image-20160921-21687-9uhkw4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/138704/original/image-20160921-21687-9uhkw4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/138704/original/image-20160921-21687-9uhkw4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/138704/original/image-20160921-21687-9uhkw4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/138704/original/image-20160921-21687-9uhkw4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/138704/original/image-20160921-21687-9uhkw4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/138704/original/image-20160921-21687-9uhkw4.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">
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<span class="caption">A volunteer receives the Ebola vaccine in a trial at Oxford University’s Jenner Institute in 2014.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/28909624750/in/photolist-ci5bjd-pWSMJH-pExryb-rg1jFL-regnn8-qAAbzs-rg2dWE-rg2dVN-rg8E4k-qFL356-9RM3aV-F94TwG-ED4YzK-v7FA9z-ushSu8-JLG2hf-p66rbs-qAAbPA-a86WX2-p66r93-xxi358-Gak68V-vXN86T-ushUQk-us863A-Lu5gjz-Lu5gjp-L3Dof3-Kx6E9E-Lu5gfr-Jbkjpq-JFU7Xd-JbkjpL">Wellcome Images/Flickr</a></span>
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<h2>A Zika vaccine is still a long way off</h2>
<p>The process is long, but recent experience shows it can be streamlined. The testing and <a href="http://www.prnewswire.com/news-releases/johnson--johnson-announces-world-health-organization-will-review-ebola-vaccine-regimen-for-emergency-use-assessment-and-listing-eual-300326319.html">emergency use</a> of Ebola vaccines occurred in a <a href="https://theconversation.com/news-about-the-success-of-a-new-ebola-vaccine-may-be-too-good-to-be-true-45801">remarkably short time</a> during the recent West African Ebola outbreak. However, we were fortunate to have <a href="http://www.nytimes.com/2014/10/24/health/without-lucrative-market-potential-ebola-vaccine-was-shelved-for-years.html?_r=0">existing Ebola vaccine products on the shelf</a> – based on research done years earlier – that could be tested again during the outbreak. </p>
<p>So, will we have a Zika vaccine in the near future? Early laboratory studies have been efficiently and rapidly conducted and have produced promising data. With multiple Phase 1 clinical trials ongoing in humans, we are progressing well into the vaccine testing process. But the long vaccine development process is focused on ensuring production of the safest and most effective vaccine for use.</p><img src="https://counter.theconversation.com/content/63804/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Robert Bednarczyk receives funding from the National Institutes of Health, the Bill and Melinda Gates Foundation, and the National Vaccine Program Office. </span></em></p>The long vaccine development process is focused on ensuring production of the safest and most effective vaccine for use.Robert Bednarczyk, Assistant Professor of Global Health and Epidemiology, Emory UniversityLicensed as Creative Commons – attribution, no derivatives.