tag:theconversation.com,2011:/us/topics/immune-memory-98374/articlesImmune memory – The Conversation2024-03-08T13:37:11Ztag:theconversation.com,2011:article/2235232024-03-08T13:37:11Z2024-03-08T13:37:11ZImmune cells can adapt to invading pathogens, deciding whether to fight now or prepare for the next battle<figure><img src="https://images.theconversation.com/files/579022/original/file-20240229-16-4ad8vr.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Understanding the flexibility of T cell memory can lead to improved vaccines and immunotherapies.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/maturing-t-lymphocyte-illustration-royalty-free-illustration/1489195717">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p>How does your immune system decide between fighting invading pathogens now or preparing to fight them in the future? Turns out, it can <a href="https://doi.org/10.1016/j.immuni.2023.12.006">change its mind</a>.</p>
<p>Every person has <a href="https://doi.org/10.1073/pnas.1409155111">10 million to 100 million unique T cells</a> that have a critical job in the immune system: patrolling the body for invading pathogens or cancerous cells to eliminate. Each of these T cells has a unique receptor that allows it to recognize foreign proteins on the surface of infected or cancerous cells. When the right T cell encounters the right protein, it rapidly forms many copies of itself to destroy the offending pathogen. </p>
<p>Importantly, this process of proliferation gives rise to both short-lived effector T cells that shut down the immediate pathogen attack and long-lived memory T cells that provide protection against future attacks. But how do T cells decide whether to form cells that kill pathogens now or protect against future infections?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of cytotoxic T cell killing a target cell" src="https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=418&fit=crop&dpr=1 600w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=418&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=418&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=526&fit=crop&dpr=1 754w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=526&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/580789/original/file-20240308-16-w72oqc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=526&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cytotoxic T cells bind to foreign proteins on infected or cancerous cells and subsequently destroy those target cells by releasing molecules like granzyme and perforin.</span>
<span class="attribution"><a class="source" href="https://pressbooks.ccconline.org/bio106/chapter/lymphatic-levels-of-organization/">Anatomy & Physiology/SBCCOE</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<p><a href="https://www.researchgate.net/scientific-contributions/Kathleen-Abadie-2232092055">We are</a> <a href="https://www.researchgate.net/scientific-contributions/Elisa-Clark-2148857839">a team</a> <a href="https://scholar.google.com/citations?user=ckyY7T8AAAAJ&hl=en">of bioengineers</a> studying how immune cells mature. In our <a href="https://doi.org/10.1016/j.immuni.2023.12.006">recently published research</a>, we found that having multiple pathways to decide whether to kill pathogens now or prepare for future invaders boosts the immune system’s ability to effectively respond to different types of challenges.</p>
<h2>Fight or remember?</h2>
<p>To understand when and how T cells decide to become effector cells that kill pathogens or memory cells that prepare for future infections, we <a href="https://doi.org/10.1016/j.immuni.2023.12.006">took movies of T cells dividing</a> in response to a stimulus mimicking an encounter with a pathogen. </p>
<p>Specifically, we tracked the activity of a gene called T cell factor 1, or TCF1. This gene is essential for the longevity of memory cells. We found that stochastic, or probabilistic, silencing of the TCF1 gene when cells confront invading pathogens and inflammation <a href="https://doi.org/10.1016/j.immuni.2023.12.006">drives an early decision</a> between whether T cells become effector or memory cells. Exposure to higher levels of pathogens or inflammation increases the probability of forming effector cells.</p>
<p>Surprisingly, though, we found that some effector cells that had turned off TCF1 early on were able to <a href="https://doi.org/10.1016/j.immuni.2023.12.006">turn it back on</a> after clearing the pathogen, later becoming memory cells. </p>
<p>Through mathematical modeling, we determined that this flexibility in decision making among memory T cells is critical to generating the right number of cells that respond immediately and cells that prepare for the future, appropriate to the severity of the infection. </p>
<h2>Understanding immune memory</h2>
<p>The proper formation of persistent, long-lived T cell memory is critical to a person’s ability to fend off diseases ranging from the common cold to COVID-19 to cancer.</p>
<p>From a <a href="https://doi.org/10.1016/0377-2217(93)E0210-O">social and cognitive science perspective</a>, flexibility allows people to adapt and respond optimally to uncertain and dynamic environments. Similarly, for immune cells responding to a pathogen, flexibility in decision making around whether to become memory cells may enable greater responsiveness to an evolving immune challenge.</p>
<p>Memory cells can be <a href="https://doi.org/10.1016/j.immuni.2018.02.010">subclassified into different types</a> with distinct features and roles in protective immunity. It’s possible that the pathway where memory cells diverge from effector cells early on and the pathway where memory cells form from effector cells later on give rise to particular subtypes of memory cells. </p>
<p>Our study focuses on T cell memory in the context of acute infections the immune system can successfully clear in days, such as cold, the flu or food poisoning. In contrast, chronic conditions such as HIV and cancer require persistent immune responses; long-lived, memory-like cells are critical for this persistence. Our team is investigating whether flexible memory decision making also applies to chronic conditions and whether we can leverage that flexibility to improve cancer immunotherapy.</p>
<p>Resolving uncertainty surrounding how and when memory cells form could help improve vaccine design and therapies that boost the immune system’s ability to provide long-term protection against diverse infectious diseases.</p>
<p><em>This article was updated to replace a figure of T cell differentiation with cytotoxic T cell activity.</em></p><img src="https://counter.theconversation.com/content/223523/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kathleen Abadie was funded by a NSF (National Science Foundation) Graduate Research Fellowships. She performed this research in affiliation with the University of Washington Department of Bioengineering. </span></em></p><p class="fine-print"><em><span>Elisa Clark performed her research in affiliation with the University of Washington (UW) Department of Bioengineering and was funded by a National Science Foundation Graduate Research Fellowship (NSF-GRFP) and by a predoctoral fellowship through the UW Institute for Stem Cell and Regenerative Medicine (ISCRM). </span></em></p><p class="fine-print"><em><span>Hao Yuan Kueh receives funding from the National Institutes of Health.</span></em></p>When faced with a threat, T cells have the decision-making flexibility to both clear out the pathogen now and ready themselves for a future encounter.Kathleen Abadie, Ph.D. Candidate in Bioengineering, University of WashingtonElisa Clark, Ph.D. Candidate in Bioengineering, University of WashingtonHao Yuan Kueh, Associate Professor of Bioengineering, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2097742023-07-19T15:02:22Z2023-07-19T15:02:22ZAsymptomatic COVID-19 is linked to a gene variant that boosts immune memory after exposure to prior seasonal cold viruses<figure><img src="https://images.theconversation.com/files/538083/original/file-20230718-33186-1uz5zq.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2429%2C1220&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetics may play a role in COVID-19 disease severity.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/virus-wide-royalty-free-image/1312985523">BlackJack3D/E+ via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>A <a href="https://www.nature.com/articles/s41586-023-06331-x">common genetic variant</a> explains why some people are asymptomatic after being infected with the virus that causes COVID-19, according to our recently published study in the journal Nature.</p>
<p>Early in the pandemic, we were intrigued that many people did not develop COVID-19 symptoms while still testing positive for it. Because asymptomatic people are unlikely to seek medical help, we knew that collecting DNA samples to study the role of genetics in asymptomatic infections would be difficult. So instead, we took advantage of existing genetic data stored in the <a href="https://bethematch.org/about-us/how-we-help-patients/be-the-match-registry/">Be The Match</a> U.S. bone marrow donor registry. </p>
<p>We invited volunteers registered as donors to track their experience with COVID-19 via a smartphone app developed by the <a href="https://covid19.eurekaplatform.org">COVID-19 Citizen Science Study</a>. This allowed us to analyze the genetics of nearly 30,000 people without collecting biological samples and to identify COVID-19 positive individuals who never became sick.</p>
<p>We were particularly interested in analyzing the variation of <a href="https://www.uptodate.com/contents/human-leukocyte-antigens-hla-a-roadmap">human leukocyte antigen, or HLA, genes</a>. These key components of the immune system encode for proteins that display the viral particles that <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">T cells</a> – a group of immune system cells critical for fighting infections – recognize. Because HLA molecules are important in the immune response to pathogens and are highly variable among people, we thought they might play a role in COVID-19.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Computer illustration of HLA-B*1501." src="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=815&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=815&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=815&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1024&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1024&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538087/original/file-20230718-18870-crqach.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1024&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">This is a 3D model of the protein that the gene variant HLA-B*15:01 codes for.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HLA_B%5E1501.png">Pdeitiker/Wikimedia Commons</a></span>
</figcaption>
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<p>We found that 1,428 unvaccinated individuals reported a positive COVID-19 test, of whom 136 reported no COVID-19 symptoms. Our analysis identified a common variant of an HLA gene <a href="https://www.nature.com/articles/s41586-023-06331-x">called <em>HLA-B*15:01</em></a> that is associated with asymptomatic infection. This variant is present in <a href="https://doi.org/10.1016/j.humimm.2013.06.025">about 10% of the population with European ancestry</a>. </p>
<p>We found that people carrying the variant were more than twice as likely to remain asymptomatic after being infected with COVID-19, and those carrying two copies of this variant were more than eight times more likely to not have any symptoms. </p>
<p>Next, we used cells from people with the HLA variant who donated blood several years before the pandemic to see whether they had preexisting immunity to the virus that causes COVID-19. We found that people who had never been exposed to COVID-19 had memory T cells that worked against a specific particle of the virus, enabling them to elicit a very effective immune response against COVID-19. We also found that, when bound to HLA, this viral particle looks very similar to fragments of seasonal coronaviruses recognized by T cells. </p>
<p>Our findings suggest that <a href="https://www.nature.com/articles/s41586-023-06331-x">preexposure to seasonal cold viruses</a> allowed people with <em>HLA-B*15:01</em> to develop a very effective immune memory that helped them to quickly kill the virus before they developed symptoms. </p>
<h2>Why it matters</h2>
<p>Identifying the genetic factors associated with how the disease progresses after infection provides the basis for understanding why people respond differently to the virus that causes COVID-19 as well as other viral illnesses. Focusing on asymptomatic infections also sheds light on the early stages of infection and how the immune system fights against COVID-19. </p>
<p>Most existing vaccines protect against severe COVID-19 symptoms. Therefore, identifying the viral fragments that mediate asymptomatic infection, such as the one we discovered, can help develop more specific vaccines or therapies for COVID-19.</p>
<h2>What still isn’t known</h2>
<p>Although the genetic association we identified is strong, the immune system is very complex. It remains unclear what other mechanisms regulate asymptomatic infections, or why not everyone carrying this specific variant remains without symptoms.</p>
<h2>What’s next</h2>
<p>We want to know if the genetic variant we identified is shared by individuals from different ancestries. This will help us understand which genetic variants are important among those in these groups with asymptomatic COVID-19. We also hope to learn what makes the cross-reactive T cells in people with <em>HLA-B*15:01</em> so remarkably effective at keeping the symptoms associated with this virus at bay.</p><img src="https://counter.theconversation.com/content/209774/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jill Hollenbach receives funding from National Institutes of Health</span></em></p><p class="fine-print"><em><span>Danillo Augusto receives funding from the National Institutes of Health</span></em></p>Researchers found that people with a specific gene variant were two to eight times more likely to not have symptoms after infection.Jill Hollenbach, Professor of Neurology, University of California, San FranciscoDanillo Augusto, Assistant Professor of Biological Sciences, University of North Carolina – CharlotteLicensed 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>
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<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>
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<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>
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<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/1642362021-08-02T05:45:02Z2021-08-02T05:45:02ZIf I’ve already had COVID, do I need a vaccine? And how does the immune system respond? An expert explains<figure><img src="https://images.theconversation.com/files/413897/original/file-20210730-13-1sp5ftm.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3600%2C2398&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Andre Coelho/EPA/AAP</span></span></figcaption></figure><p>Over a year into the pandemic, questions around immune responses after COVID continue to confound. </p>
<p>One question many people are asking is whether the immunity you get from contracting COVID and recovering is enough to protect you in the future.</p>
<p>The answer is no, it’s not. </p>
<p>Here’s why.</p>
<h2>Remind me, how does our immune response work?</h2>
<p>Immune responses are innate or acquired. Innate, or short-term immunity, occurs when immune cells that are the body’s first line of defence are activated against a pathogen like a virus or bacteria.</p>
<p>If the pathogen is able to cross the first line of defence, T-cells and B-cells are triggered into action. B-cells fight through secreted proteins called antibodies, specific to each pathogen. T-cells can be categorised into helper T-cells and killer T-cells. Helper T-cells “help” B-cells in making antibodies. Killer T-cells directly kill infected cells. </p>
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<p>Once the battle is over, B-cells and T-cells develop “memory” and can recognise the invading pathogen next time. This is known as acquired or adaptive immunity, which triggers long-term protection. </p>
<p>What happens when you get reinfected? Memory B-cells don’t just produce identical antibodies, they also produce antibody variants. These diverse set of antibodies form an elaborate security ring to fight SARS-CoV-2 variants. </p>
<h2>Natural immunity is not enough</h2>
<p>Getting COVID and recovering (known as “natural infection”) <a href="https://www.smh.com.au/national/vaccines-recommended-over-natural-immunity-against-covid-variants-20210706-p5876s.html">doesn’t appear</a> to generate protection as robust as that generated after vaccination.</p>
<p>And the immune response generated post-infection and vaccination, known as hybrid immunity, is <a href="https://doi.org/10.1126/science.abg9175">more potent</a> than either natural infection or vaccination alone.</p>
<p>People who have had COVID and recovered and <a href="https://doi.org/10.1126/science.abj2258">then been vaccinated against COVID</a> have more diverse and high-quality memory B-cell responses than people who’ve just been vaccinated.</p>
<p><a href="https://science.sciencemag.org/content/372/6549/1413">Studies</a> indicate mRNA vaccines generate a more potent immune response with previous infection, at least <a href="https://science.sciencemag.org/content/372/6549/1418">against some variants</a> including Alpha and Beta.</p>
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<p>And studies have shown that antibody levels <a href="https://science.sciencemag.org/content/372/6549/1413">were higher</a> among those who’d recovered from COVID and were subsequently vaccinated than those who’d only had the infection.</p>
<p>Memory B-cells against the coronavirus have been reported to be <a href="https://science.sciencemag.org/content/372/6549/1413">five to ten times higher</a> in people vaccinated post-infection than natural infection or vaccination alone.</p>
<h2>Is one dose enough after COVID?</h2>
<p><a href="https://science.sciencemag.org/content/372/6549/1418">Some reports</a> have suggested people who’ve had COVID need only one dose of the vaccine. Clinical trials of approved vaccines <a href="https://science.sciencemag.org/content/372/6549/1418">didn’t generate</a> relevant data because people who’d already had COVID were excluded from phase 3 trials.</p>
<p><a href="https://science.sciencemag.org/content/372/6549/1413">One study from June</a> showed people with previous exposure to SARS-CoV-2 tended to mount powerful immune responses to a single mRNA shot. They didn’t gain much benefit from a second jab.</p>
<p>A single dose of an mRNA vaccine after infection achieves similar levels of antibodies against the spike protein’s receptor binding domain (which allows the virus to attach to our cells) compared to double doses of vaccination in people never exposed to SARS-CoV-2.</p>
<p>We need more studies to fully understand how long memory B-cell and T-cell responses will last in both groups.</p>
<p>Also, a single dose strategy has only been studied for mRNA-based vaccines. More data is required to understand whether one jab post-infection would be effective for all the vaccines.</p>
<p>At this stage, it’s still good to have both doses of a COVID vaccine after recovering from COVID.</p>
<h2>Does Delta change things?</h2>
<p>The development of new vaccines must <a href="https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003656">keep pace</a> with the evolution of the coronavirus.</p>
<p>At least one variant seems to have evolved enough to overtake others, Delta, which is about <a href="https://doi.org/10.1038/d41586-021-01696-3">60% more transmissible</a> than the Alpha variant. Delta is <a href="https://doi.org/10.1038/d41586-021-01696-3">moderately resistant</a> to vaccines, meaning it can reduce how well the vaccines work, particularly in people who’ve only had one dose.</p>
<p>There’s <a href="https://www.nature.com/articles/d41586-021-01696-3">no data available yet</a> about how effective a single jab is for people who were previously infected with Delta and recovered.</p>
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Read more:
<a href="https://theconversation.com/why-is-delta-such-a-worry-its-more-infectious-probably-causes-more-severe-disease-and-challenges-our-vaccines-163579">Why is Delta such a worry? It's more infectious, probably causes more severe disease, and challenges our vaccines</a>
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<p>The most important thing you can do to protect yourself from Delta is to get fully vaccinated.</p>
<p>According to a Public Health England report, one dose of Pfizer offered <a href="https://doi.org/10.1038/d41586-021-01696-3">only about 33% protection</a> against symptomatic disease with Delta, but two doses was 88% effective. Two doses was also 96% effective against hospitalisation from Delta. The AstraZeneca vaccine was 92% effective against hospitalisation from Delta after two doses. </p>
<p>A few vaccine manufacturers, including Pfizer, are now planning to use a potential third dose as a booster to combat the Delta variant.</p><img src="https://counter.theconversation.com/content/164236/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sunit K. Singh 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>Recovering from COVID and then getting vaccinated, known as hybrid immunity, is more potent than being infected or vaccinated alone.Sunit K. Singh, Professor of Molecular Immunology and Virology, Institute of Medical Sciences, Banaras Hindu UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1575992021-03-24T18:51:58Z2021-03-24T18:51:58ZDo I still need to get a COVID vaccine if I’ve had coronavirus?<p>The COVID vaccine rollout is underway, with Australians lining up to get their jabs. But what if you have already had COVID-19? Is it still a good idea to get vaccinated?</p>
<p>Although natural exposure to the virus stimulates immunity, we don’t yet know how long this immunity will last. And people will vary in their ability to mount a protective immune response.</p>
<p>Even if you’ve had COVID-19, you should still get vaccinated. A COVID vaccine may offer more reliable and sustained immunity than a previous infection. At the very least, it will add an extra layer of targeted protection.</p>
<p>Here’s how our immune response works after a natural infection versus a vaccine.</p>
<h2>From B cells to neutralising antibodies</h2>
<p>Soon after becoming infected with SARS-CoV-2 (the virus that causes COVID-19), our immune cells (T cells and B cells) activate. Activated B cells produce so-called <a href="https://www.news-medical.net/health/What-are-Neutralizing-Antibodies.aspx">neutralising antibodies</a>. These antibody-secreting cells defend our bodies against the infection by making antibodies that bind to spikes on the virus surface, and block the virus from entering our cells. </p>
<p>Neutralising antibodies spill over into the bloodstream and travel around the body looking to mop up virus. After the infection has resolved, these activated B cells calm down and transition to a resting state. They move from our blood to our lymph nodes and bones. These so-called <a href="https://pubmed.ncbi.nlm.nih.gov/32978311/">memory B cells</a> survive for decades, along with help from memory T cells. </p>
<p>But they need a nudge once in a while to ensure they’re ready to kick into gear if we’re exposed to an infection.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?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">
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<span class="caption">SARS-CoV-2 viral particles have surface spikes (in green), to which antibodies attach.</span>
<span class="attribution"><span class="source">NIAID/flickr</span></span>
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<h2>Our immune cells rely on memory</h2>
<p>When we’re re-exposed to a virus, or receive a vaccine booster, these memory cells awaken, become activated and produce large amounts of antibodies much faster. This immune memory reduces the risk we’ll become infected with SARS-CoV-2. But if we do, it allows for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608032/">quicker healing from COVID-19</a>.</p>
<p>Sustained <a href="https://www.nature.com/articles/s41467-020-20247-4">neutralising antibody levels</a> indicate a good degree of protection against SARS-CoV-2. How long we hang onto natural immunity after COVID-19 is variable and depends on <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899649/">viral, human and environmental factors</a>. For example, the viral variant can make a difference, along with our genes, underlying health conditions, and age.</p>
<p>These factors can affect our neutralising antibody levels, which can wane over time to dip below protective levels. </p>
<p>As COVID-19 hasn’t been around for a particularly long time, it’s difficult to know how long natural immunity generally lasts. However, antibodies and immune memory appear to last for <a href="https://pubmed.ncbi.nlm.nih.gov/32964627/">at least two months</a>.</p>
<p>For patients who have recovered from SARS, a related coronavirus, research has shown they maintained <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/">antibodies for up to two to three years</a> following infection. </p>
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Read more:
<a href="https://theconversation.com/the-second-phase-of-australias-covid-vaccine-rollout-is-underway-despite-a-rocky-start-heres-what-you-need-to-know-157426">The second phase of Australia's COVID vaccine rollout is underway, despite a rocky start. Here's what you need to know</a>
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<h2>Immune responses to a vaccine</h2>
<p>Again, because of the short time frame, we have limited data on sustained antibody responses following vaccination. But immunity appears to be strong <a href="https://pubmed.ncbi.nlm.nih.gov/33617777/">three months after</a> the Oxford/AstraZeneca vaccine. </p>
<p>With COVID-19 vaccines, certain variable factors have been targeted, in a way they can’t with natural infections. For example, considerations like the dose size and the time between doses are all established to confer optimal immunity.</p>
<p>As we continue to monitor people who have received the COVID vaccines, we’ll develop a better understanding of protective immunity and its longevity. </p>
<h2>Staying on top of variants</h2>
<p>Natural immunity from infection may protect against other variants to some degree, but vaccines will play a crucial role as the virus continues to mutate.</p>
<p>It may be necessary to get regular <a href="https://theconversation.com/why-do-we-need-booster-shots-and-could-we-mix-and-match-different-covid-vaccines-155951">boosters</a> of the COVID vaccine until the pandemic is under control. This will provide protection against variants our pre-existing antibodies may not be able to neutralise. </p>
<p>Boosters enhance our broad immunity to parts of the spike proteins shared between different virus variants. Antibodies produced to these common regions can neutralise the virus and stop infection. </p>
<p>We saw this to a limited extent in people who had common cold infections with <a href="https://pubmed.ncbi.nlm.nih.gov/32978311/">other coronaviruses</a> before COVID-19. </p>
<h2>Only one jab? Vaccines as a cure for long COVID?</h2>
<p>There’s been some research suggesting people who have had COVID may only need <a href="https://jamanetwork.com/journals/jama/fullarticle/2777171">one dose of the vaccine</a> to be protected. </p>
<p>For people who have had COVID, one dose may serve to top up their antibodies to protective levels. This is because they’re starting on a stronger footing in terms of their antibody levels and immune memory, compared to people who haven’t had the virus.</p>
<p>But experts in Australia still recommended <a href="https://www.abc.net.au/news/health/2021-03-23/covid-19-people-who-have-had-it-may-need-one-dose-vaccine/13252338">two doses</a>, regardless of whether you’ve had COVID.</p>
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Read more:
<a href="https://theconversation.com/why-well-get-covid-booster-vaccines-quickly-and-how-we-know-theyre-safe-156120">Why we'll get COVID booster vaccines quickly and how we know they're safe</a>
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<p>Meanwhile, reports have indicated people experiencing <a href="https://www.abc.net.au/news/health/2021-03-24/coronavirus-long-covid-could-the-vaccine-cure-it/100023114">long COVID</a> may also benefit from vaccination. We’re not sure how this happens, but symptoms may improve with clearance of any hidden virus reservoirs from the body. Research into this phenomenon is ongoing.</p>
<p>At the end of the day, when the vaccine is available to you, you should get vaccinated, even if you’ve had COVID-19. While the vaccine is likely to protect you, it’s also important to protect others, as we look towards a goal of herd immunity.</p><img src="https://counter.theconversation.com/content/157599/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Cassandra Berry 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>People who have had COVID will still benefit from having a COVID vaccine. Here’s why.Cassandra Berry, Professor of Immunology, Murdoch UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1550962021-02-12T19:03:22Z2021-02-12T19:03:22ZMystery of how human immune cells develop lifelong immunity uncovered – new research<figure><img src="https://images.theconversation.com/files/384031/original/file-20210212-13-854phd.jpg?ixlib=rb-1.1.0&rect=15%2C0%2C5229%2C3483&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Our research could be important for developing more effective vaccines in the future.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-giving-patient-vaccine-flu-shot-1498605842">Arturs Budkevics/ Shutterstock</a></span></figcaption></figure><p>We understand much of how the immune system works but, as recent efforts to combat COVID-19 have shown, its sheer complexity means many mysteries <a href="https://www.theatlantic.com/health/archive/2020/08/covid-19-immunity-is-the-pandemics-central-mystery/614956/">still remain</a>. For example, how our immune system learns to remember past infections has proved very difficult to study in humans. But our <a href="https://immunology.sciencemag.org/content/6/56/eabe6291">new study</a> has brought us one step closer to understanding how our body remembers past infections so we can fight them in the future. We uncovered the important role antibodies play in creating long-lived immunity – and that different types of immune cells, called B cells, can influence the type of immune memory generated.</p>
<p>Our research focused on so-called <a href="https://www.cell.com/cell/fulltext/S0092-8674(19)30278-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867419302788%3Fshowall%3Dtrue">germinal centres</a> which form during infections in our lymph nodes, spleen, and tonsils. These play an important role in our immune system, as they’re where immune cells assemble and interact during immune responses. They’re also where our “immune memory” is created, so the immune system can “remember” how to defend against certain pathogens in the future.</p>
<p>Germinal centres are made up of different immune cells, and one type, called B cells, are particularly important for generating immune memory. These B cells make antibodies (a protein) in response to infections or vaccinations, which bind to pathogens (like bacteria and viruses) and either destroy them or trigger other immune cells into action. </p>
<p>Early on in an infection, some of our body’s B cells respond by releasing a burst of antibodies that provide an early line of defence against the pathogen. But most of these B cells released in this initial first wave are short-lived and die once the infection is over, resulting in the loss of their antibodies. However, some B cells enter germinal centres where they can evolve stronger antibodies and become long-lived cells that protect us from future infection.</p>
<h2>Germinal centres</h2>
<p>Although the germinal centre is incredibly important to immune memory, its complexity has made it very difficult for scientists to completely understand how B cells behave while inside them. So we set out to create a “roadmap” of the germinal centre response using human tonsils to understand which types of B cells are present, and how their behaviour contributes to creating long-lived immunity. Knowing these factors could be important for developing effective vaccines.</p>
<p>We used a cutting-edge technology called <a href="https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0960-x">single cell genomics</a>, which measures the genes expressed by tens of thousands of individual cells and the genetic sequence that produces their antibody. The genes expressed by each individual B cell tells us about the cell’s behaviour and function, while the antibody gene sequence reveals how the antibodies change in the germinal centre. This approach allowed us to identify very rare types of B cells that would be missed with other technologies. </p>
<p>We then used this information to reconstruct the entire <a href="https://www.tonsilimmune.org/">germinal centre response</a>, which showed us exactly how different B cells evolve from the moment they detect a pathogen through to immune memory formation. </p>
<h2>Antibody class</h2>
<p>One of our key discoveries was that the type of antibody a B cell makes affects how it behaves and how likely it is to create long-lived immunity. B cells can express one of five antibody classes, and each class triggers different immune responses. For example, the antibody class IgG triggers strong antiviral immune responses, while the IgA class protects our gut and airway. </p>
<figure class="align-center ">
<img alt="Computer generated image of Y-shaped antibodies surrounding a large sphere-shaped pathogen." src="https://images.theconversation.com/files/384013/original/file-20210212-15-1imbe1y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/384013/original/file-20210212-15-1imbe1y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/384013/original/file-20210212-15-1imbe1y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/384013/original/file-20210212-15-1imbe1y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/384013/original/file-20210212-15-1imbe1y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/384013/original/file-20210212-15-1imbe1y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/384013/original/file-20210212-15-1imbe1y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Different types of antibodies target certain pathogens.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antibody-immunoglobulin-yshaped-protein-produced-mainly-1670732119">ustas7777777/ Shutterstock</a></span>
</figcaption>
</figure>
<p>All B cells start off making the antibody class IgM, which offers broad immune protection, but is less effective compared to other classes. But B cells can switch to another class when they are activated during an immune response. It was previously thought that this process of class switching occurs in the germinal centre. But recent studies in mice have found B cells switch their antibody class before the <a href="https://www.cell.com/immunity/fulltext/S1074-7613(19)30317-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761319303176%3Fshowall%3Dtrue">germinal centre response</a>. We were able to confirm this happens in humans as well. We also identified which genes are expressed by B cells at this important stage. </p>
<p>We also found that B cells that had switched from making IgM to IgA or IgG antibodies express different levels of certain genes, including genes that control whether a B cell becomes long-lived. So, whether a B cell switches its antibody class before entering a germinal centre influences whether it develops long-lived immunity to that particular pathogen. However, we still don’t completely understand why a B cell switches or not.</p>
<p>Whether a B cell is part of the short-lived first wave or helps form the germinal centre also depends on many factors, including how quickly a pathogen is cleared, a person’s age, and the type of infection. Because B cells need germinal centres to develop immune memory, the more we can discover about these different factors, the better our understanding of our susceptibility to different diseases. </p>
<p>Understanding precisely how germinal centres work is key to designing effective vaccines that generate lifelong immunity. In the future, combining different technologies such as those we used in our study with <a href="https://www.nature.com/articles/s41591-020-01145-0">other methods</a> would allow us to directly compare immune responses to vaccines against many infectious agents, like the coronavirus SARS-CoV-2, and understand immune memory, more generally.</p><img src="https://counter.theconversation.com/content/155096/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr Louisa James receives funding from the Wellcome Trust and Bart's Charity. She is affiliated with the British Society for Immunology. </span></em></p><p class="fine-print"><em><span>Hamish King is a recipient of the Sir Henry Wellcome Post Doctoral Fellowship from the Wellcome Trust.</span></em></p>We mapped the genes of B cells to better understand why some develop immunity and others don’t.Louisa James, Lecturer in Immunology, Queen Mary University of LondonHamish King, Sir Henry Wellcome Fellow, Centre of Immunobiology, Queen Mary University of LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1528492021-01-11T14:48:57Z2021-01-11T14:48:57ZCOVID-19 immunity: how long does it last?<p>Millions of people across the world have been infected with SARS-CoV-2, the virus that causes COVID-19. Countries are also now embarking on <a href="https://ourworldindata.org/covid-vaccinations">massive vaccination campaigns</a> to control the virus and protect their most vulnerable citizens. One of the biggest questions remaining is whether vaccination and/or prior infection with SARS-CoV-2 offers lasting protection against this deadly virus. The good news is that immunology is at last revealing some clues.</p>
<p>To understand whether immunity is possible – and why this has even been questioned – it is important to consider the nature of SARS-CoV-2. It is a betacoronavirus, and several betacoronaviruses already circulate widely in humans – they are most familiar to us as a cause of the common cold. However, immunity to cold-causing viruses is not long-lasting, leading many researchers to question whether longer term immunity to SARS-CoV-2 is possible.</p>
<p>However, studies considering the closely related betacoronaviruses that cause the diseases <a href="https://www.nature.com/articles/s41467-020-18450-4">Mers</a> and <a href="https://www.sciencedirect.com/science/article/pii/S1074761320303125">Sars</a> offer a glimmer of hope. With these viruses, immunity has proved more durable. Could this be true for immunity to SARS-CoV-2 too?</p>
<h2>Well-trained protection</h2>
<p>The first of the body’s immune cells to respond to an infection are designed to attack the invading substances to try to control the infection’s spread and limit the damage done. The immune cells that respond later that are responsible for immunity are known as lymphocytes, which include <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">B cells and T cells</a>. Lymphocytes need time to learn to identify the threat that they are facing, but once trained they can be rapidly deployed to seek and destroy the virus. </p>
<p>Our T cells and B cells work together to combat infection, but they have quite different functions that enable them to deal with a huge variety of threats. B cells make antibodies that neutralise infections. T cells are broadly divided into two types – T helper cells and cytotoxic T cells. Cytotoxic T cells directly kill viruses and cells that viruses have infected. T helper cells support the functioning of B cells and cytotoxic T cells. Collectively these are known as “effector” cells.</p>
<figure class="align-center ">
<img alt="Virus cell in the body being attacked by tiny antibodies." src="https://images.theconversation.com/files/378008/original/file-20210111-15-1obb130.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/378008/original/file-20210111-15-1obb130.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/378008/original/file-20210111-15-1obb130.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/378008/original/file-20210111-15-1obb130.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/378008/original/file-20210111-15-1obb130.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/378008/original/file-20210111-15-1obb130.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/378008/original/file-20210111-15-1obb130.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">B cells, once trained to identify a threat, create antibodies specific to that threat that help destroy it.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-leukocyte-seclude-antibodies-648506539">Christoph Burgstedt/Shutterstock</a></span>
</figcaption>
</figure>
<p>Studies have now demonstrated the <a href="https://immunology.sciencemag.org/content/5/54/eabf3698">critical role</a> that these effector cells play in the fight against COVID-19. Once the infection is gone, these cells should then die off in order to avoid causing excessive damage in the body. </p>
<p>But some effector cells persist. In an <a href="https://www.biorxiv.org/content/10.1101/2020.11.01.362319v1">early piece of research</a> yet to be reviewed by other scientists, functional T cells have been detected six months after infection. Similarly, even patients who have had <a href="https://europepmc.org/article/med/33296701">mild COVID-19</a> have detectable antibodies six to nine months <a href="https://pubmed.ncbi.nlm.nih.gov/18716625/">after infection</a>. However, antibodies do wane over time, so these antibodies against SARS-CoV-2 could eventually disappear.</p>
<h2>Remembering the danger</h2>
<p>Such discoveries raise real optimism about protection from reinfection. But what happens if or when effector lymphocyte levels finally drop off? Well, our immune system has another trick up its sleeve to protect us for the long term, even after people’s effector cells and antibody levels have fallen. Once lymphocytes have been trained to deal with a virus, a pool of the cells remember it and are kept for the future. These “memory” cells can then be rapidly deployed if the threat is encountered again. </p>
<p>Memory cells are incredibly powerful tools for our immune system and can be very long-lived, with studies showing memory B cells for smallpox persisting at least 60 years after <a href="https://www.jimmunol.org/content/171/10/4969?ijkey=01bbf74a445bc6caed34f72ea0c7e477f66609df&keytype2=tf_ipsecsha">vaccination</a> and for Spanish flu at least 90 years after the <a href="https://pubmed.ncbi.nlm.nih.gov/18716625/">1918 pandemic</a>. In order to understand whether long-term immunity to SARS-CoV-2 is possible, it’s therefore critical to consider not just effector cells but all types of memory cells – B, T helper and cytotoxic T memory cells.</p>
<p>Fortunately, memory cells can be identified by specific structures and proteins that they express on their surfaces, enabling researchers to distinguish them from effector cells. Now that COVID-19 has been with us for a year, researchers are becoming able to make great leaps in understanding about memory responses to COVID-19. Evidence is emerging of <a href="https://science.sciencemag.org/content/early/2021/01/05/science.abf4063">memory T cell responses</a> lasting six to nine months after infection, and a recent preprint study (yet to be reviewed by other scientists) has also identified what appear to be <a href="https://www.biorxiv.org/content/10.1101/2020.11.03.367391v1">memory B cell responses</a>. </p>
<p>Studies have also been investigating whether prior exposure to the virus confers protection, with <a href="https://www.journalofinfection.com/article/S0163-4453(20)30781-7/fulltext">research</a> showing that in the UK’s second wave, previously infected health workers were either completely protected from reinfection or were asymptomatic if they picked up the virus again. Such observational studies give real hope for the durability and potential of protective immunity.</p>
<p>We still have much to learn about the immunology of COVID-19, but the pace of research is astounding, and the more we learn, the more we are empowered to beat this virus. Our immune system is incredibly powerful, and these studies showing persistent immune responses nine months after infection are real cause for celebration. They give us confidence that, with vaccination, we have a real chance to win the war against COVID-19.</p><img src="https://counter.theconversation.com/content/152849/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sheena Cruickshank 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>Long-term protection will depend on the ‘memory response’ developed by our immune systems – and the initial signs are promising.Sheena Cruickshank, Professor in Biomedical Sciences, University of ManchesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1526722021-01-11T13:15:58Z2021-01-11T13:15:58ZDelaying second COVID-19 vaccine doses will make supplies last longer but comes with risks<figure><img src="https://images.theconversation.com/files/377814/original/file-20210108-17-i9rw6u.jpg?ixlib=rb-1.1.0&rect=7%2C0%2C5080%2C3323&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Health care workers wait in line for vaccinations at a site in Los Angeles. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/jan-6-2021-health-care-workers-wait-in-line-for-news-photo/1230475202?adppopup=true">Xinhua News Agency via Getty Images</a></span></figcaption></figure><p>Drugmakers are facing <a href="https://pink.pharmaintelligence.informa.com/PS143400/Pfizers-Expected-2020-COVID19-Vaccine-Production-Fell-By-50-After-Scaleup-Delays">challenges</a> in manufacturing vaccines and building supply chains to meet the demand for COVID-19 vaccines. <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-supply-us-100-million-additional-doses">Pfizer has even lowered</a> production targets. Scarcity of vaccines has prompted calls for a Band-Aid-like strategy to <a href="https://www.nytimes.com/2020/12/18/opinion/coronavirus-vaccine-doses.html">stretch the precarious supply</a>. </p>
<p>To protect as many people as possible from COVID-19, the U.K.’s medical officers <a href="https://www.health-ni.gov.uk/news/statement-uk-chief-medical-officers-prioritisation-first-doses-covid-19-vaccines">have chosen</a> to prioritize distribution of a first vaccine dose to as many people as possible – by delaying the second doses of the Pfizer/BioNTech COVID vaccine up to 12 weeks from the recommended 3-4. <a href="https://www.nytimes.com/2021/01/08/world/biden-vaccine.html">President-elect Biden wants to release all vaccine doses</a> to speed up the vaccination program – but the risk is that vaccine makers won’t be able to replenish the supply to make sure that the second dose is delivered on time.</p>
<p>These decisions have <a href="https://www.cnn.com/2021/01/01/health/uk-vaccine-doses-chief-medical-officers-intl/index.html">opened up a rift</a> between <a href="https://www.bmj.com/content/372/bmj.n18">experts</a> because <a href="https://www.nytimes.com/2020/12/18/opinion/coronavirus-vaccine-doses.html">some support giving a single vaccine dose</a> to as many people as possible, while <a href="https://www.cnn.com/videos/health/2021/01/01/fauci-coronavirus-vaccine-second-dose-sot-vpx-nr.cnn">others want to vaccinate according to the protocol</a> used during the clinical trials. In the U.S. only around <a href="https://www.washingtonpost.com/business/2020/12/05/operation-warp-speed-coronavirus-vaccine-shortfall/">a 10th</a> of the 300 million doses promised <a href="https://www.hhs.gov/about/news/2020/05/21/trump-administration-accelerates-astrazeneca-covid-19-vaccine-to-be-available-beginning-in-october.html#:%7E:text=Responding%20to%20President%20Trump's%20call,called%20AZD1222%2C%20with%20the%20first">by January</a> under Operation Warp Speed are actually available. Nevertheless, the Food and Drug Administration has <a href="https://www.fda.gov/news-events/press-announcements/fda-statement-following-authorized-dosing-schedules-covid-19-vaccines">reminded the medical community</a> of the importance of receiving both doses of COVID-19 vaccines in line with the way they were tested in clinical trials. The FDA says there is no data that demonstrates vaccine efficacy if the second dose is delayed.</p>
<p>I’m interested in this debate because I coordinate an international <a href="https://clinicaltrials.gov/ct2/show/NCT04354701">registry of patients with cancer</a> who have been diagnosed with COVID-19. Patients with current or prior cancers are <a href="https://doi.org/10.1158/2159-8290.cd-20-1817">twice as likely</a> to die from COVID-19 than those without cancer. The Centers for Disease Control and Prevention has not included current or surviving cancer patients for inclusion in the <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations.html">first group of COVID-19 vaccine recipents</a>. Altering vaccine doses seems an easy fix to stretch limited supplies and provide vaccines for more vulnerable populations. But is it the right thing to do?</p>
<h2>What is a vaccine?</h2>
<p>A <a href="https://www.cdc.gov/vaccines/hcp/conversations/downloads/vacsafe-understand-color-office.pdf">vaccine</a> gives the human body a glimpse of the disease-causing virus. This preview trains the immune system for exposure to the real virus. Early vaccines, like the <a href="https://www.cdc.gov/vaccines/vpd/polio/public/index.html">oral poliovirus vaccines</a>, contained <a href="https://vaccine-safety-training.org/live-attenuated-vaccines.html">live but weakened</a> viruses. These provide robust immunity but carry a small risk of illness because even a weakened virus can become active and cause disease in rare cases. </p>
<p>Modern vaccines are safer because they increasingly rely on only parts of the virus, called antigens. In the case of COVID-19, the antigen is the <a href="https://pdb101.rcsb.org/motm/246">spike protein</a> that enables the SARS-CoV-2 virus to enter cells. <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html">Various COVID-19 vaccines</a> under development are based on a synthetic spike protein or its genetic code. </p>
<p>The FDA has so far given <a href="https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs">emergency use authorization</a> to two <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-based COVID-19 vaccines;</a> from <a href="https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine">Moderna</a> and <a href="https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine">Pfizer-BioNTech</a>. In the U.K., a DNA vaccine created by <a href="https://theconversation.com/oxford-astrazeneca-vaccine-is-cheaper-than-pfizers-and-modernas-and-doesnt-require-supercold-temperature-150697">AstraZeneca</a> is <a href="https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca/information-for-healthcare-professionals-on-covid-19-vaccine-astrazeneca">also authorized</a>. These three vaccines supply the genetic material that encodes the viral spike protein. After injection in the upper arm, the muscle cells read the genetic instructions and use them to make the viral spike protein directly in the body. </p>
<p>The downside to these safer, newer vaccines is that a single dose triggers a less effective immune response than a weakened virus vaccine and often requires <a href="https://www.cdc.gov/vaccines/hcp/conversations/downloads/vacsafe-understand-color-office.pdf">repeated vaccinations to get more complete immunity</a>. Many current human vaccines, such as against <a href="https://www.cdc.gov/vaccines/hcp/vis/vis-statements/td.html">tetanus</a>, <a href="https://www.cdc.gov/hepatitis/hbv/vaccadults.htm">hepatitis B</a>, <a href="https://www.cdc.gov/measles/vaccination.html">measles</a>, <a href="https://www.cdc.gov/vaccines/vpd/polio/index.html">polio</a> and <a href="https://www.cdc.gov/vaccines/vpd/hpv/public/index.html">HPV</a>, require two doses: the first to prime the immune system and the second to boost the immune response.</p>
<p>Efficacy of all three authorized COVID-19 vaccines was studied in the two-dose regimens. For the Pfizer-BioNTech COVID-19 vaccine, the studied and approved interval is <a href="https://www.fda.gov/media/144245/download">21 days</a> between the first and second dose. For the Moderna COVID-19 vaccine, the interval is <a href="https://www.fda.gov/media/144434/download">28 days</a>. For the AstraZeneca vaccine, the trial is for two doses <a href="https://doi.org/10.1016/S0140-6736(20)32661-1">28 days</a> apart. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/377816/original/file-20210108-19-yhxtte.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/377816/original/file-20210108-19-yhxtte.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/377816/original/file-20210108-19-yhxtte.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=395&fit=crop&dpr=1 600w, https://images.theconversation.com/files/377816/original/file-20210108-19-yhxtte.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=395&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/377816/original/file-20210108-19-yhxtte.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=395&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/377816/original/file-20210108-19-yhxtte.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=496&fit=crop&dpr=1 754w, https://images.theconversation.com/files/377816/original/file-20210108-19-yhxtte.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=496&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/377816/original/file-20210108-19-yhxtte.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=496&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In clinical trials, the two doses of the Pfizer/BioNTech vaccine were taken three weeks apart. This led to 95% efficacy against the COVID-19 virus.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/concepts-of-mrna-vaccine-for-coronavirus-royalty-free-illustration/1285089812?adppopup=true">iStock/Getty Images Plus</a></span>
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<h2>What happens after vaccination?</h2>
<p>An effective vaccine should produce immunological memory similar to or better than what is acquired by exposure to the natural disease – but without causing the disease. To do so, <a href="https://www.who.int/immunization/documents/Elsevier_Vaccine_immunology.pdf">after the first exposure</a>, from a vaccine or a natural infection, a <a href="https://theconversation.com/declining-antibodies-and-immunity-to-covid-19-why-the-worry-143323">class of white blood cells</a> called the naïve B cells produce antibodies as the first line of defense against infection. </p>
<p>These early antibodies reach peak levels usually four weeks after the first immunization but decline significantly thereafter. Fewer antibodies means it’s more likely that invading virus particles can escape destruction. So the protective immunity from the first or prime vaccination dose is generally not very effective or durable. </p>
<p>After the first exposure, some B cells and another type of <a href="https://theconversation.com/declining-antibodies-and-immunity-to-covid-19-why-the-worry-143323">white blood cell</a> called T cells become “memory” cells that remember the antigen – in this case the spike protein. On second and subsequent booster exposures, these memory cells quickly reactivate to produce more potent antibodies that are able to recognize and bind to the target virus tightly. The antibodies produced by memory cells after the booster dose rise rapidly at tens to hundreds-fold higher protective levels and persist longer. </p>
<h2>Why is the timing of the second dose important?</h2>
<p>Both mRNA vaccines, even after the first dose, offer protection well above the <a href="https://www.fda.gov/media/142749/download">50% minimum threshold</a> set for emergency use authorization criteria for COVID-19 vaccines based on the clinical trials. But the efficacy of these vaccines was tested in a two-dose regimen. </p>
<figure class="align-right ">
<img alt="Gloved hand holding two syringes." src="https://images.theconversation.com/files/377819/original/file-20210108-15-8xg7or.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/377819/original/file-20210108-15-8xg7or.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/377819/original/file-20210108-15-8xg7or.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/377819/original/file-20210108-15-8xg7or.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/377819/original/file-20210108-15-8xg7or.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/377819/original/file-20210108-15-8xg7or.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/377819/original/file-20210108-15-8xg7or.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&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">In clinical trials the volunteers received two doses of the vaccine 3-4 weeks apart. Will immunity be complete if the second dose is delayed?</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/doctors-hand-with-a-syringe-of-covid-19-coronavirus-royalty-free-image/1216432557?adppopup=true">Jose A. Bernat Bacete/Moment/Getty Images</a></span>
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<p>During Pfizer-BioNTech’s vaccine trial, one vaccinated participant and nine who received a placebo developed a severe case of COVID-19 after the first dose. This suggests that <a href="https://www.fda.gov/media/144245/download">participants developed partial protection</a> as early as 12 days after the first dose. However, all vaccine recipients eventually received their second dose just nine days later, so the data does not exist for how long the protection from the single dose would have lasted. </p>
<p>Similarly, for <a href="https://www.fda.gov/media/144434/download">Moderna’s vaccine trial</a>, there appeared to be some protection against COVID-19 following one dose; but the limited data does not provide sufficient information about longer-term protection beyond 28 days after the single dose. </p>
<p>In the absence of supporting evidence, nothing definitive can be concluded about the depth or duration of protection after just a single dose of currently authorized vaccines, or choosing between the studied and longer gaps between doses.</p>
<p>While the efficacy of the mRNA COVID-19 vaccines against symptomatic COVID-19 has exceeded expectations, researchers still do not know how long that protection lasts. In the <a href="https://doi.org/10.1056/NEJMc2032195">follow-up of the phase 1 trial of Moderna’s vaccine</a> during the 119 days after the first dose, the antibodies declined in all participants and the neutralizing antibodies – which not only bind the virus but also block infection – fell 50% to 75% in the people older than 56. </p>
<h2>What can happen if vaccination is incomplete?</h2>
<p>Viruses naturally mutate because of copying errors in their genetic code as they multiply in the host’s body, or due to swapping of genetic codes between different viruses co-infecting the same host. </p>
<p>But they also evolve to evade the immunity of the host, specially if competing against weak but sustained immune response. SARS-CoV-2 can already lie low in infected individuals, and approximately <a href="https://doi.org/10.7326/M20-3012">40% to 45% of those infected display no symptoms at all</a>. In an immunocompromised patient – using therapies to fight autoimmune disease or cancer – the virus has been found to be present for <a href="https://doi.org/10.1056/nejmc2031364">up to 154 days</a>. In such situations there are increased odds that a virus variant can emerge that can escape the immune response and spread fast. Indeed, it is suspected that the new highly infectious <a href="https://doi.org/:10.1001/jama.2020.27124">U.K. variant</a>, which is <a href="https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html">also spreading in the U.S.</a>, could have <a href="https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563">originated</a> in a chronically infected individual. </p>
<p>Although evolution of vaccine resistance is considered <a href="https://doi.org/10.1016/j.mib.2012.08.002">very rare</a> because of effective and rigorously developed vaccines, <a href="https://doi.org/10.1098/rspb.2003.2664">mathematical modeling</a> suggests that a resistant virus can readily arise if immune response is too weak to destroy all the viruses in the host. </p>
<p>Rushed and ineffective vaccines can produce antibodies that fail to recognize and bind viruses poorly, which <a href="https://www.nature.com/articles/nm0109-21">can do more harm than good</a>. </p>
<p>Changing the dosing to overcome supply shortages is a contentious and ongoing debate. However, making wrong decisions without adequate scientific evidence could be counterproductive.</p><img src="https://counter.theconversation.com/content/152672/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sanjay Mishra receives funding from the National Cancer Institute (NCI) and has previously received support from the National Institutes of Health (NIH). </span></em></p>With vaccine shortages looming, experts are debating whether it is important to receive two doses or whether it’s better to give one dose to more people and give a second when the supply is better.Sanjay Mishra, Project Coordinator & Staff Scientist, Vanderbilt University Medical Center, Vanderbilt UniversityLicensed as Creative Commons – attribution, no derivatives.