tag:theconversation.com,2011:/au/topics/flu-virus-5796/articlesFlu virus – The Conversation2023-04-23T20:04:31Ztag:theconversation.com,2011:article/2041192023-04-23T20:04:31Z2023-04-23T20:04:31ZFlu or COVID? You can now test for both at home with a single swab. Here’s what you need to know<figure><img src="https://images.theconversation.com/files/522244/original/file-20230421-22-d7zbfx.jpg?ixlib=rb-1.1.0&rect=2%2C5%2C995%2C660&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/young-sick-woman-home-african-lying-1631753728">Shutterstock</a></span></figcaption></figure><p>If you have respiratory symptoms as we head towards winter and flu season, could it be COVID or the flu? Or something else entirely?</p>
<p>Now, we have a <a href="https://www.sbs.com.au/news/article/combination-flu-and-covid-rapid-tests-have-hit-store-shelves-how-useful-are-they/pmh4bx4rk">range of home tests</a> that can distinguish between flu and COVID with one swab. They use technology you might be used to. They’re rapid antigen tests or RATs.</p>
<p>Here’s what you need to know about the tests, why they might be useful, and what they don’t tell us.</p>
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<h2>What’s new about these tests?</h2>
<p>Most people were introduced to RATs while testing at home for COVID.</p>
<p>But RATs to detect the flu have been available for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156320/">years</a>, albeit used by health workers to test patients.</p>
<p>The latest RATs are different for two reasons. One, they detect both COVID and flu with one swab (a “combo” test). Two, they can be used at home.</p>
<p>The first of these combo home tests for flu/COVID was approved in <a href="https://www.tga.gov.au/news/media-releases/first-combination-covid-19-and-influenza-self-tests-approved-australia">September 2022</a>. Now several are on the market.</p>
<p>These tests let you check, with one test kit, if you are infected with two types of flu (influenza A and B) and SARS-CoV-2 (the virus that causes COVID).</p>
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Read more:
<a href="https://theconversation.com/are-flu-cases-already-100-times-higher-than-last-year-heres-what-we-really-know-about-the-2023-flu-season-201559">Are flu cases already 100 times higher than last year? Here's what we really know about the 2023 flu season</a>
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<h2>How do they work?</h2>
<p>These RATs contain antibodies that can detect influenza A, influenza B, and SARS-CoV-2.</p>
<p>Some kits have a test cassette with one well to add drops to and one window labelled: C (control), A (influenza A), B (influenza B) and T (test for COVID). </p>
<p>Some tests have two wells and two test windows. You view the influenza results in one window and the COVID results in the other.</p>
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<a href="https://images.theconversation.com/files/522242/original/file-20230421-14-aaner7.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Test cassette of combined flu/COVID rapid antigen test" src="https://images.theconversation.com/files/522242/original/file-20230421-14-aaner7.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/522242/original/file-20230421-14-aaner7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=603&fit=crop&dpr=1 600w, https://images.theconversation.com/files/522242/original/file-20230421-14-aaner7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=603&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/522242/original/file-20230421-14-aaner7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=603&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/522242/original/file-20230421-14-aaner7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=757&fit=crop&dpr=1 754w, https://images.theconversation.com/files/522242/original/file-20230421-14-aaner7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=757&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/522242/original/file-20230421-14-aaner7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=757&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 test cassettes have two wells, like this one.</span>
<span class="attribution"><a class="source" href="https://www.tga.gov.au/sites/default/files/2023-02/covid-19-rapid-antigen-self-tests-are-approved-australia-ifu-404854_0.pdf">TGA</a></span>
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<p>In the influenza window you will see markings C, A and B. If a line becomes visible at A (and C), you have tested positive for influenza A. If a line becomes visible at B (and C), you are positive for influenza B. If lines are visible at A, B and C you have tested positive for both influenza A and B. </p>
<p>If either A or B has a line but not C, or if none of them do, the test is invalid and you will need to take a new one. </p>
<p>The COVID window works the same way as in a standard RAT for COVID. If a line becomes visible at C and T, you are COVID-positive. If there is a line at C but not T, you are COVID-negative. If there is no line at C the test is invalid. </p>
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Read more:
<a href="https://theconversation.com/is-my-rat-actually-working-how-to-tell-if-your-covid-test-can-detect-omicron-196210">Is my RAT actually working? How to tell if your COVID test can detect Omicron</a>
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<h2>Why take the test? 3 reasons</h2>
<p>If you have respiratory symptoms, there are some practical reasons for knowing whether you are positive for COVID or flu. </p>
<p>One, if you know you have COVID, this will affect the timing of your booster vaccine. The Australian Technical Advisory Group on Immunisation recommends adults wait <a href="https://www.health.gov.au/news/atagi-2023-booster-advice">six months</a> after a COVID infection to get a booster to increase the time you have protective immunity. So it helps to know if you have been infected.</p>
<p>Two, if you need antiviral treatment, the medications differ depending on whether you have <a href="https://www.ncbi.nlm.nih.gov/books/NBK459363/">flu</a> or <a href="https://www.nps.org.au/radar/articles/nirmatrelvir-and-ritonavir-paxlovid-for-mild-to-moderate-covid-19">COVID</a>. </p>
<p>Three, knowing you have flu or COVID means you can take steps to protect others. This could mean working at home, avoiding contact with vulnerable people, and wearing a mask in company.</p>
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<a href="https://images.theconversation.com/files/522245/original/file-20230421-22-f0mwfd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Woman's holding Paxlovid pill in one hand, glass of water in other, Paxlovid, thermometer in background" src="https://images.theconversation.com/files/522245/original/file-20230421-22-f0mwfd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/522245/original/file-20230421-22-f0mwfd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/522245/original/file-20230421-22-f0mwfd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/522245/original/file-20230421-22-f0mwfd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/522245/original/file-20230421-22-f0mwfd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/522245/original/file-20230421-22-f0mwfd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/522245/original/file-20230421-22-f0mwfd.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">If you know you have COVID, you may be eligible for antiviral treatment.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/female-taking-paxlovid-prescription-treating-covid19-2161258693">MargJohnsonVA/Shutterstock</a></span>
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<h2>Which test to use? When to use it?</h2>
<p>The Therapeutic Goods Administration (TGA) lists <a href="https://www.tga.gov.au/products/covid-19/covid-19-tests/covid-19-rapid-antigen-self-tests-home-use/covid-19-rapid-antigen-self-tests-are-approved-australia">approved tests</a> on its website. Type the term “combination” in the search box. All combo tests currently listed use nasal swabs to collect the sample.</p>
<p>Most are listed as “very high sensitivity”. This means they get the same result in detecting positive cases as the gold standard PCR test 95% of the time. The others have “high sensitivity” (90% agreement with a PCR).</p>
<p>The <a href="https://www.tga.gov.au/qas-combination-rapid-antigen-self-tests">best time</a> to take the test is within four days of developing symptoms, as this is when it is easiest to detect both flu and COVID. The tests are more reliable if <a href="https://www.tga.gov.au/qas-combination-rapid-antigen-self-tests">you have symptoms</a>. </p>
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Read more:
<a href="https://theconversation.com/15-things-not-to-do-when-using-a-rapid-antigen-test-from-storing-in-the-freezer-to-sampling-snot-176364">15 things not to do when using a rapid antigen test, from storing in the freezer to sampling snot</a>
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<h2>What if I have symptoms but the test is negative?</h2>
<p>One possibility is that your viral load was not high enough to be detected. You could take another test a day or so later to check again.</p>
<p>Another is you may have a different virus. Viruses that cause respiratory symptoms include <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553670/">rhinoviruses</a>, adenoviruses, <a href="https://www.health.gov.au/diseases/respiratory-syncytial-virus-rsv-infection">respiratory syncytial virus</a> and <a href="https://journals.lww.com/pidj/Fulltext/2022/03000/Proving_Etiologic_Relationships_to_Disease_.18.aspx">common cold coronaviruses</a>. </p>
<p>Other pathogens (disease-causing microorganisms) or health conditions can also cause respiratory symptoms. If you are concerned, consult your doctor for medical advice. </p>
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Read more:
<a href="https://theconversation.com/havent-had-covid-or-a-vaccine-dose-in-the-past-six-months-consider-getting-a-booster-199096">Haven't had COVID or a vaccine dose in the past six months? Consider getting a booster</a>
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<h2>What else should I know?</h2>
<p>As each test differs, make sure you <a href="https://theconversation.com/15-things-not-to-do-when-using-a-rapid-antigen-test-from-storing-in-the-freezer-to-sampling-snot-176364">follow the instructions</a> for that specific test.</p>
<p>The price of combo kits advertised online varies from A$8.95 to $59 (excluding delivery) so it pays to shop around.</p>
<p>It’s worth trying to avoid catching the flu rather than testing for it later. Flu vaccination reduces your chances of catching the flu by <a href="https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm">40-60%</a> when the vaccine is well matched to circulating strains. Flu vaccines for the 2023 flu season are available now.</p><img src="https://counter.theconversation.com/content/204119/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Thea van de Mortel teaches into the Master of Infection Prevention and Control program at Grififth University. </span></em></p>Knowing if you have COVID or the flu can affect when you get vaccinated, need a particular antiviral, or if you need to work from home. But these combination tests can be expensive.Thea van de Mortel, Professor, Nursing, School of Nursing and Midwifery, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1812332022-06-02T12:17:20Z2022-06-02T12:17:20ZFuture COVID-19 booster shots will likely need fresh formulations as new coronavirus variants of concern continue to emerge<figure><img src="https://images.theconversation.com/files/466619/original/file-20220601-48323-a2yi45.jpg?ixlib=rb-1.1.0&rect=685%2C319%2C6350%2C4931&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Viral surveillance and prediction may be key parts of figuring out what goes into a vaccine.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/close-up-of-syringe-with-bottles-on-table-pakistan-royalty-free-image/1342313994">Pexels Cover/500px via Getty Images</a></span></figcaption></figure><p>Being up to date on COVID-19 vaccines means having <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html">had three or four doses</a> of the same shot at this point. Current boosters are the same formulations as the first authorized shots, <a href="https://www.nature.com/articles/d41586-021-02854-3">based on the original strain of the coronavirus</a> that emerged in late 2019. <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/work.html">They do still protect</a> against severe COVID-19, hospitalizations and deaths. But as immunity wanes over time and new, more contagious SARS-CoV-2 variants emerge, the world needs a long-term boosting strategy.</p>
<p><a href="https://scholar.google.com/citations?user=v61MWbsAAAAJ&hl=en&oi=ao">I’m an immunologist</a> who studies immunity to viruses. I was a part of the teams that <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">helped develop the Moderna</a> and <a href="https://theconversation.com/how-does-the-johnson-and-johnson-vaccine-compare-to-other-coronavirus-vaccines-4-questions-answered-155944">Johnson & Johnson SARS-CoV-2 vaccines</a>, and <a href="https://theconversation.com/what-monoclonal-antibodies-are-and-why-we-need-them-as-well-as-a-vaccine-149356">the monoclonal antibody therapies</a> from Eli Lilly and AstraZeneca.</p>
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<a href="https://images.theconversation.com/files/466621/original/file-20220601-48889-avwg9y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="out of focus smiling woman extends her arm holding vaccination record card" src="https://images.theconversation.com/files/466621/original/file-20220601-48889-avwg9y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/466621/original/file-20220601-48889-avwg9y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=692&fit=crop&dpr=1 600w, https://images.theconversation.com/files/466621/original/file-20220601-48889-avwg9y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=692&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/466621/original/file-20220601-48889-avwg9y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=692&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/466621/original/file-20220601-48889-avwg9y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=870&fit=crop&dpr=1 754w, https://images.theconversation.com/files/466621/original/file-20220601-48889-avwg9y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=870&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/466621/original/file-20220601-48889-avwg9y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=870&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">How many lines will ultimately be filled out on your COVID-19 vaccination card?</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/vaccination-cart-royalty-free-image/1347369341">LPETTET/E+ via Getty Images</a></span>
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<p>I often get asked how frequently, or infrequently, I think people are likely to need COVID-19 booster shots in the future. No one has a crystal ball to see which SARS-CoV-2 variant will come next or how good future variants will be at evading vaccine immunity. But looking to other respiratory viral foes that have troubled humanity for a while can suggest what the future could look like. </p>
<p>Influenza virus provides one example. It’s endemic in humans, meaning it hasn’t disappeared and continues to cause recurrent seasonal waves of infection in the population. Every year officials try to predict the best formulation of a flu shot to reduce the risk of severe disease.</p>
<p>As SARS-CoV-2 continues to evolve and is <a href="https://theconversation.com/is-covid-19-here-to-stay-a-team-of-biologists-explains-what-it-means-for-a-virus-to-become-endemic-168462">likely to become endemic</a>, it is possible people may need periodic booster shots for the foreseeable future. I suspect scientists will eventually need to update the COVID-19 vaccine to take on newer variants, as they do for flu.</p>
<h2>Forecasting flu, based on careful surveillance</h2>
<p>Influenza virus surveillance offers a potential model for how SARS-CoV-2 could be tracked over time. Flu viruses have caused several pandemics, including the one in 1918 that killed <a href="https://theconversation.com/10-misconceptions-about-the-1918-flu-the-greatest-pandemic-in-history-133994">an estimated 50 million people worldwide</a>. Every year there are seasonal outbreaks of flu, and every year officials encourage the public to <a href="https://www.cdc.gov/flu/prevent/flushot.htm">get their flu shots</a>.</p>
<p>Each year, health agencies including the World Health Organization’s <a href="https://www.who.int/initiatives/global-influenza-surveillance-and-response-system">Global Influenza Surveillance and Response System</a> make an educated guess based on the flu strains circulating in the Southern Hemisphere about which ones are most likely to circulate in the Northern Hemisphere’s upcoming flu season. Then large-scale vaccine production begins, based on the selected flu strains.</p>
<p>Some flu seasons, the vaccine doesn’t turn out to be a <a href="https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html">great match with the virus strains</a> that end up circulating most widely. Those years, the shot is not as good at preventing severe illness. While this prediction process is far from perfect, the flu vaccine field has benefited from strong viral surveillance systems and a concerted international effort by public health agencies to prepare.</p>
<p>While the particulars for influenza and SARS-CoV-2 viruses are different, I think the COVID-19 field should think about adopting similar surveillance systems in the long term. Staying on top of what strains are circulating will help researchers update the SARS-CoV-2 vaccine to match up-to-date coronavirus variants.</p>
<h2>How SARS-CoV-2 has evolved so far</h2>
<p>SARS-CoV-2 faces an evolutionary quandary as it reproduces and spreads from person to person. The virus needs to maintain its ability to get into human cells using its spike protein, while still changing in ways that allow it to evade vaccine immunity. Vaccines are designed to get your body to recognize a particular spike protein, so the more it changes, the higher the chance that the vaccine will be ineffective against the new variant.</p>
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<p>Despite these challenges, SARS-CoV-2 and its variants have successfully evolved to be more transmissible and to better evade people’s immune responses. Over the course of the COVID-19 pandemic, a <a href="https://www.theatlantic.com/science/archive/2022/03/new-covid-variant-mitigation/626980/">new SARS-CoV-2 variant of concern has emerged and dominated</a> transmission in a series of contagion waves every four to seven months. Almost like clockwork, the D614G variant emerged in the spring of 2020 and overtook the original SARS-CoV-2 outbreak strain. In late 2020 and early 2021, the alpha variant emerged and dominated transmission. In mid-2021, the delta variant overtook alpha and then dominated transmission until it was displaced by the omicron variant at the end of 2021.</p>
<p>There’s no reason to think this trend won’t continue. In the coming months, the world may see a dominant <a href="https://www.bloomberg.com/news/articles/2022-04-30/omicron-sublineages-can-evade-antibodies-from-earlier-infections">descendant of the various omicron subvariants</a>. And it’s certainly possible a new variant will emerge from a nondominant pool of SARS-CoV-2, which is how omicron itself came to be.</p>
<p>Current booster shots are simply additional doses of the vaccines based on the outbreak SARS-CoV-2 virus strain that has long been extinct. The coronavirus variants have changed a lot from the original virus, which doesn’t bode well for continued vaccine efficacy. The idea of tailor-made annual shots – like the flu vaccine – sounds appealing. The problem is that scientists haven’t yet been able to predict what the next SARS-CoV-2 variant will be with any degree of confidence.</p>
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<a href="https://images.theconversation.com/files/466624/original/file-20220601-48861-v4usft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="people walk near a tent marked 'Vaccines | Boosters'" src="https://images.theconversation.com/files/466624/original/file-20220601-48861-v4usft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/466624/original/file-20220601-48861-v4usft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/466624/original/file-20220601-48861-v4usft.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/466624/original/file-20220601-48861-v4usft.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/466624/original/file-20220601-48861-v4usft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/466624/original/file-20220601-48861-v4usft.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/466624/original/file-20220601-48861-v4usft.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">Periodic booster shots may be in order for the foreseeable future.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/covid-vaccine-and-testing-site-is-set-up-outside-of-yankee-news-photo/1390355456">Spencer Platt/Getty Images</a></span>
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<h2>Planning for the future</h2>
<p>Yes, the dominant SARS-CoV-2 variants in the upcoming fall and winter seasons may look different from the omicron subvariants currently circulating. But an updated booster that more closely resembles today’s omicron subvariants, coupled with the immunity people already have from the first vaccines, will likely offer better protection going forward. It might require less frequent boosting – at least as long as omicron sublineages continue to dominate.</p>
<p>The Food and Drug Administration is set to meet in the coming weeks to decide what the fall boosters should be in time for manufacturers to produce the shots. Vaccine makers like Moderna are currently testing their booster candidates in people and <a href="https://thehill.com/policy/healthcare/3473235-moderna-expects-large-amounts-of-omicron-booster-available-by-fall/">evaluating the immune response against newly emerging variants</a>. The test results will likely decide what will be used in anticipation of a fall or winter surge. </p>
<p>Another possibility is to pivot the vaccine booster strategy to include universal coronavirus vaccine approaches that already look promising in animal studies. Researchers are working toward what’s called a universal vaccine which would be effective against multiple strains. Some focus on <a href="https://doi.org/10.1126/science.abi4506">chimeric spikes</a>, which fuse parts of the spike of different coronaviruses together in one vaccine, to broaden protective immunity. <a href="https://clinicaltrials.gov/ct2/show/NCT04784767">Others are experimenting with</a> <a href="https://doi.org/10.1038/s41586-021-03594-0">nanoparticle vaccines</a> that get the immune system to focus on the most vulnerable regions within the coronavirus spike.</p>
<p>These strategies have been shown to ward off difficult-to-stop SARS-CoV-2 variants in lab experiments. They also work in animals against the original SARS virus that caused an outbreak in the early 2000s as well as zoonotic coronaviruses from bats that could jump into humans, causing a future SARS-CoV-3 outbreak.</p>
<p>Science has provided multiple safe and effective vaccines that reduce the risk of severe COVID-19. Reformulating booster strategies, either toward universal-based vaccines or updated boosters, can help steer us out of the COVID-19 pandemic.</p><img src="https://counter.theconversation.com/content/181233/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David R. Martinez receives funding from the National Institutes of Health, the Howard Hughes Medical Institute, and the Burroughs Wellcome Fund.</span></em></p>A new generation of vaccines and boosters against SARS-CoV-2 may take a page from the anti-influenza playbook, with shots periodically tailored to target the most commonly circulating virus strains.David R. Martinez, Postdoctoral Fellow in Epidemiology, University of North Carolina at Chapel HillLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1522742021-01-27T20:47:01Z2021-01-27T20:47:01ZA universal influenza vaccine may be one step closer, bringing long-lasting protection against flu<figure><img src="https://images.theconversation.com/files/380969/original/file-20210127-13-1m5xbho.jpg?ixlib=rb-1.1.0&rect=0%2C17%2C3586%2C2640&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Wouldn't it be nice if one shot could protect you for life?</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/woman-walks-past-free-flu-shot-advertisements-outside-of-news-photo/1228109098">Bryan R. Smith/AFP via Getty Images</a></span></figcaption></figure><p>A bad year for flu can mean <a href="https://www.cdc.gov/flu/about/burden/past-seasons.html">tens of thousands</a> of deaths in the U.S. <a href="https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-dashboard.html">Getting vaccinated</a> can protect you from influenza, but you have to get the shot every year to catch up with <a href="https://doi.org/10.1038/nrmicro.2017.118">the changing virus</a> and to top up the <a href="https://www.sciencemag.org/news/2019/04/how-long-do-vaccines-last-surprising-answers-may-help-protect-people-longer">short-lived immunity the vaccine provides</a>. The vaccine’s effectiveness also depends on correct predictions about which strains will be most common in a given season. </p>
<p>For these reasons, a one-and-done universal vaccine that would provide lasting immunity over multiple flu seasons and protect against a variety of strains has been a long-term goal for scientists.</p>
<p>Researchers are now one step closer to hitting that target. Scientists recently completed the first human trial of a vaccine created by recombinant genetic technology to fool the immune system into attacking a part of the virus that does not change so fast and is common among different strains.</p>
<p>I am a microbiologist <a href="https://theconversation.com/a-massive-public-health-effort-eradicated-smallpox-but-scientists-are-still-studying-the-deadly-virus-139468">interested in infectious diseases</a>, and I’ve followed the <a href="https://theconversation.com/this-year-the-flu-came-in-two-waves-heres-why-117053">seasonal flu epidemic for several years</a>. I’m excited by this news, which could mark the turning point in the quest for a universal flu vaccine. Here’s how it all works.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="cross section of influenza virus showing RNA and surface proteins" src="https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.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"></a>
<figcaption>
<span class="caption">3D model of an influenza virus. Its genetic material is inside, with proteins – HA in blue, NA in red – poking out from the surface.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/computer-generated-3d-model-showing-a-cross-section-of-the-news-photo/976723030">Smith Collection/GadoArchive Photos via Getty Images</a></span>
</figcaption>
</figure>
<h2>Biology of the invading influenza virus</h2>
<p>Like the virus that causes COVID-19, the influenza virus has a protein shell that is coated by a lipid membrane. Sticking through the membrane are multiple copies of three types of proteins: haemagglutinin, abbreviated as HA; neuraminidase, abbreviated as NA; and the matrix protein, M2.</p>
<p>It’s the properties of the <a href="https://www.cdc.gov/flu/about/viruses/types.htm">HA and NA proteins</a> that distinguish the different strains of the virus. You’ve probably heard of strains like H1N1 and H3N2, both of which are <a href="https://www.cdc.gov/flu/weekly/index.htm">infecting people in the U.S. this year</a>. </p>
<p>The HA molecule is shaped a bit like a flower bud, with a stalk and a head. Once someone inhales the virus, the <a href="https://doi.org/10.1101/cshperspect.a038778">tip of the HA molecule’s head binds</a> to a receptor on the surface of the cells that line the person’s respiratory passages.</p>
<p>This initial binding is crucial as it induces the cell to engulf the virus. Once inside, the virus gets to work replicating its own genetic material. But the enzyme that copies its single-strand RNA <a href="https://doi.org/10.1128/JVI.00694-10">is very sloppy</a>; it can leave two or three mistakes, called mutations, <a href="https://doi.org/10.7554/eLife.26437">in every new copy</a>.</p>
<p>Sometimes the genetic changes are so drastic that the progeny viruses don’t survive; other times they are the start of new flu strains. Based on <a href="https://nextstrain.org/flu/seasonal/h1n1pdm/ha/2y?l=clock">viral samples collected from around the world</a>, the flu virus that arrives one year will have about seven new mutations in the gene for HA and four in the gene for NA compared to the previous year’s virus. These differences are a big part of why the same influenza vaccine won’t be as effective from one year to the next.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Immune cells fighting off flu with antibodies" src="https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Computer illustration of an immune cell (left) releasing many antibodies (white) to attack and disable invading flu particles.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/immune-response-to-a-virus-illustration-royalty-free-illustration/724237117">Juan Gaertner/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>Fighting off a flu infection</h2>
<p>When infected with the flu virus, your immune system produces antibodies to fend it off. <a href="https://doi.org/10.3389/fimmu.2019.02997">Most of these antibodies interact with the HA head</a> and prevent the virus from getting into your cells.</p>
<p>But there’s a downside to that strong reaction. Because the immune response to the virus’s head is so vigorous, it pays little attention to <a href="https://doi.org/10.3389/fimmu.2019.02997">other parts of the virus</a>. That means that your immune system is not prepared to fend off any future infection with a virus that has a different HA head, even if the rest of the virus is identical.</p>
<p>Current flu vaccines are inactivated versions of the influenza virus and so also work by inducing antibodies targeted to the HA head. And that’s why each version of the vaccine usually works only against a particular strain. But, as the flu spreads, the rapid rate of genetic change can produce new versions of the HA head that will evade the antibodies induced by the vaccine. These newly resistant viruses will then render even the current season’s vaccine ineffective. </p>
<p>The stalk portion of the HA molecule is much more genetically stable than the head. And HA stalks from different flu strains are much more alike than their head regions are.</p>
<p>So, an obvious way to protect people against different flu strains would be to use just the HA stalk in a vaccine. Unfortunately vaccination with only a headless stalk doesn’t seem to prevent infection. </p>
<p>Scientists are currently pursuing several <a href="https://doi.org/10.3389/fimmu.2019.02997">different solutions to this problem</a>.</p>
<h2>A new kind of flu vaccine</h2>
<p>A team of scientists led by <a href="https://labs.icahn.mssm.edu/krammerlab/dr-krammer/">Florian Krammer</a> at the Icahn School of Medicine at Mount Sinai just completed the first human <a href="https://clinicaltrials.gov/ct2/show/NCT03300050">clinical trial</a> of what they hope will be a universal flu vaccine.</p>
<p>The researchers used recombinant genetic technology to create <a href="https://doi.org/10.1038/s41591-020-1118-7">flu viruses with “chimeric” HA proteins</a> – essentially a patchwork quilt built from pieces of different flu strains.</p>
<p>Volunteers for the <a href="https://doi.org/10.1038/s41591-020-1118-7">clinical trial</a> received two vaccinations separated by three months. The first dose consisted of an inactivated H1N1 virus with its original HA stalk but the head portion from a bird influenza virus. Vaccination with this virus induced a mild antibody response to the foreign head, and a robust response to the stalk. This pattern meant that the immune systems of the subjects had never encountered the head before, but had seen the stalk from previous flu vaccinations or infections.</p>
<p>The second vaccination consisted of the same H1N1 virus but with an HA head from a different bird virus. This dose elicited, again, a mild antibody response to the new head, but a further boost in response to the HA stalk. After each vaccine dose the subjects’ stalk antibody concentrations averaged about eight times higher than their initial levels.</p>
<p>Researchers found that even though the vaccine was based on the HA stalk of the H1N1 virus strain, the antibodies it elicited reacted to HA stalks from other strains too. In lab tests, the antibodies from vaccinated volunteers attacked the H2N2 virus that caused the <a href="https://www.cdc.gov/flu/pandemic-resources/1957-1958-pandemic.html">1957 Asian flu pandemic</a> and the H9N2 virus that the CDC considers to be of <a href="https://www.cdc.gov/flu/pandemic-resources/monitoring/viruses-concern.html">concern for future outbreaks</a>. The antibodies did not react to the stalk of the more distantly related H3 viral strain.</p>
<p>The antibody response also lasted a long time; after a year and a half, the volunteers still had about four times the concentration of antibodies to the HA stalk in their blood as when the trial started.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="surface of influenza virus with HA proteins sticking out" src="https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.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">Avoiding the vigorous immune response to the protein’s head means the immune cells can concentrate on the more stable stalk of the protein.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/flu-virus-illustration-royalty-free-illustration/713781829">Kateryna Kon/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p>Since this was a <a href="https://theconversation.com/from-the-research-lab-to-your-doctors-office-heres-what-happens-in-phase-1-2-3-drug-trials-138197">phase 1 clinical trial</a> testing only for adverse effects (which were minimal), the researchers didn’t expose vaccinated people to the flu to test if their new antibodies protected them.</p>
<p>However, they did inject the subjects’ blood serum, which contains the antibodies, into mice to see if it would protect them against the flu virus. Getting a shot of serum taken from volunteers a month after receiving the booster shot, when antibody levels were high, led to mice being 95% healthier after virus exposure than mice who got blood serum from nonvaccinated volunteers. Even the mice who received serum that was collected from vaccinated volunteers a year after the start of the trial were about 30% less sick.</p>
<p><a href="https://doi.org/10.1038/s41591-020-1118-7">These results</a> show that vaccination with a chimeric flu protein can provide long-lasting immunity to several different strains of the influenza virus. Scientists will need to <a href="https://doi.org/10.1093/infdis/jiy103">continue optimizing this approach</a> so it works for different types and strains of influenza. But the success of this first human trial means you may one day get a single shot and, at last, be free from the flu.</p>
<p>[<em>The Conversation’s science, health and technology editors pick their favorite stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-favorite">Weekly on Wednesdays</a>.]</p><img src="https://counter.theconversation.com/content/152274/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patricia L. Foster is affiliated with the Union of Concerned Scientists and Concerned Scientists at Indiana University. </span></em></p>You need a new shot every year because current flu vaccines provide limited and temporary protection. But researchers’ new strategy could mean a one-and-done influenza vaccine is on the way.Patricia L. Foster, Professor Emerita of Biology, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1475162020-10-13T11:35:25Z2020-10-13T11:35:25ZExisting medicines could help improve immune function in vulnerable older adults<figure><img src="https://images.theconversation.com/files/363150/original/file-20201013-15-dwjfvl.jpg?ixlib=rb-1.1.0&rect=17%2C0%2C5734%2C3837&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Our immune cells become less able to fight off infections as we get older.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/covid19-horizontal-concept-60s-70s-years-1738937144">Viktoriia Hnatiuk/ Shutterstock</a></span></figcaption></figure><p>As we age, every major organ system progressively declines – including the <a href="https://pubmed.ncbi.nlm.nih.gov/32757035/">immune system</a>. Ageing causes our immune cells to become less able to fight off infections. This leaves older people <a href="https://pubmed.ncbi.nlm.nih.gov/6763306/">hundreds of times more vulnerable</a> to diseases such as pneumonia and flu than younger people. But the poor immune response of many older adults also reduces their ability to benefit from vaccinations designed to protect them. In fact, <a href="https://www.sciencedirect.com/science/article/pii/S0264410X05009552">research shows</a> that most older people don’t respond <a href="https://pubmed.ncbi.nlm.nih.gov/21880118/">nearly as well</a> to vaccines as younger people. While 70-90% of younger adults make a protective response to the influenza virus when given a flu vaccination, this can drop to under 20% in those over the age of 60. </p>
<p>Even before the pandemic, about one third of older people died from <a href="https://pubmed.ncbi.nlm.nih.gov/6763306/">infectious diseases</a>. Immune system deterioration also means that viruses long held dormant in the body (such as chicken pox) can become active again, compromising their quality of life. Put simply, older adults’ immune systems are just too “tired” to <a href="https://pubmed.ncbi.nlm.nih.gov/18431075/">do their job</a>.</p>
<p>But researchers have discovered that drugs which already exist can actually <a href="https://theconversation.com/anti-ageing-drugs-are-coming-an-expert-explains-102792">slow and reverse</a> both ageing and immune system decline. These effects were first observed in 2009 when mice were treated with low doses of the drug <a href="https://pubmed.ncbi.nlm.nih.gov/30096787/">rapamycin</a>. Originally developed as an antifungal, rapamycin inhibits mTOR, a protein that acts as the major cell nutrient sensor and regulates protein synthesis. Inhibiting mTOR makes it easier for cells to recyce damaged proteins, which could potentially improve their function.</p>
<p>The mice treated with rapamycin were shown to live between <a href="https://pubmed.ncbi.nlm.nih.gov/25968226/">between 15-25% longer</a> than those not taking the drug. They also showed <a href="https://science.sciencemag.org/content/342/6160/789.full">improved function</a> in many – but not all – organ systems, including the <a href="https://pubmed.ncbi.nlm.nih.gov/22587563/">immune system</a>.</p>
<p>The next step was then to determine if the drug could also improve the human immune system. In 2012 researchers using a variant of rapamycin (called everolimus) gave six-week, low-dose courses of the drug to elderly volunteers. These were safe and well tolerated, and the team found treatment enhanced participants’ immune response to flu vaccinations by <a href="https://pubmed.ncbi.nlm.nih.gov/25540326/">about 20%</a>. </p>
<p>Further studies using similar short courses of everolimus (and related drugs) revealed that volunteers taking them had about half the rate of infections <a href="https://pubmed.ncbi.nlm.nih.gov/29997249/">for a year after treatment</a> compared to those who weren’t treated. The researchers also found that treatment with everolimus had increased the activity of certain genes that play a critical role in the immune response to viruses.</p>
<p>However, rapamycin is not the only drug that improves immune function. Part of the reason our immune system deteriorates as we age is because our thymic function rapidly declines – especially in <a href="https://pubmed.ncbi.nlm.nih.gov/11589313/">older males</a>. The thymus is a key organ in the immune system as it allows the maturation of the special T cells that regulate immune responses and direct other types of immune cells to attack invading pathogens. Ageing reduces thymic function meaning fewer mature T cells are produced. But the hormone interleukin-7 can actually restore thymic function, increasing T cell output. </p>
<p>Following promising studies in <a href="https://pubmed.ncbi.nlm.nih.gov/11160192/">mice</a> researchers treated primates with interleukin-7, then vaccinated them against the flu. These animals showed <a href="https://pubmed.ncbi.nlm.nih.gov/17378748/">enhanced responses to flu vaccines</a> suggesting that further trials in humans are warranted. </p>
<figure class="align-center ">
<img alt="Older man receiving a vaccination." src="https://images.theconversation.com/files/363155/original/file-20201013-19-1tpew1g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/363155/original/file-20201013-19-1tpew1g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/363155/original/file-20201013-19-1tpew1g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/363155/original/file-20201013-19-1tpew1g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/363155/original/file-20201013-19-1tpew1g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/363155/original/file-20201013-19-1tpew1g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/363155/original/file-20201013-19-1tpew1g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">These medicines may be able to improve immune response to vaccines.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-unrecognizable-doctor-doing-vaccination-elderly-1591182001">Prostock-studio/ Shutterstock</a></span>
</figcaption>
</figure>
<p>However, small changes to the way we deliver vaccines might also have the potential to improve immune responsiveness in the most vulnerable. The time of day can actually impact immune response in humans – including our ability to make antibodies. Recently, one study of over 270 people over 65 were randomised to receive a <a href="https://pubmed.ncbi.nlm.nih.gov/27129425/">morning or afternoon vaccination</a> at their GP’s surgery for three flu strains. Somewhat better immune responses were produced by patients treated in the morning compared to those treated later in the day. The reason for this difference may be because the human “body clock” (which regulates many of our body’s functions, from whether we feel tired or awake, or whether we’re hungry) becomes increasingly <a href="https://pubmed.ncbi.nlm.nih.gov/32733482/">erratic with ageing</a>.</p>
<p>Crucially, in the context of a pandemic and with an ageing population, rapamycin, everolimus and other members of this family of drugs are already licensed for a range of uses (including vein malformation and preventing organ rejection). This means that they are safe and could, in principle, be prescribed immediately. However, while initial studies have demonstrated efficacy, they were primarily undertaken to determine the best dose for patients. Researchers now need to test these drugs on a large scale to see whether they’re equally effective in enhancing immunity in large populations and specific subgroups (such as people with other existing health conditions, including liver and heart disorders).</p>
<p>But because the enhancement of immune function seen is general – rather than dependent on being given a specific vaccine – such drugs could reduce sickness and death from multiple pathogens in a single treatment. And since some of these drugs are both <a href="https://bnf.nice.org.uk/medicinal-forms/sirolimus.html">relatively cheap</a> and already routinely available, repurposing them to help the most vulnerable populations fight off infections could save lives.</p><img src="https://counter.theconversation.com/content/147516/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Faragher serves on the scientific advisory board of the Longevity Vision Fund and is a member of the Board of Directors of the American Federation for Aging Research (AFAR). </span></em></p>These drugs may help slow or reverse immune system decline.Richard Faragher, Professor of Biogerontology, University of BrightonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1213472019-10-22T13:58:17Z2019-10-22T13:58:17ZFlu jab: for asthmatics, avoiding the flu vaccine could be a fatal mistake<figure><img src="https://images.theconversation.com/files/296251/original/file-20191009-3846-1ehmg8o.jpg?ixlib=rb-1.1.0&rect=0%2C16%2C5463%2C3620&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/success?u=http%3A%2F%2Fdownload.shutterstock.com%2Fgatekeeper%2FW3siZSI6MTU3MDY2MDA3MywiYyI6Il9waG90b19zZXNzaW9uX2lkIiwiZGMiOiJpZGxfMTQ0NDIyNDg1NyIsImsiOiJwaG90by8xNDQ0MjI0ODU3L2h1Z2UuanBnIiwibSI6MSwiZCI6InNodXR0ZXJzdG9jay1tZWRpYSJ9LCI4d3FyZEJjQjNOb2p2WHNwZDA3c2p1MHQwSzAiXQ%2Fshutterstock_1444224857.jpg&pi=33421636&m=1444224857&src=zxauk90U9BpkKLx7cBHulQ-1-0">shutterstock/1000 Words</a></span></figcaption></figure><p>It’s that time of year again, flu season is just around the corner and with it comes the dreaded fear of catching the virus. The flu can come on very quickly and <a href="https://www.nhs.uk/conditions/flu/">symptoms include</a> aching muscles, chills and sweats, a persistent headache as well as a dry, cough – along with fatigue and weakness.</p>
<p>The flu vaccine becomes available just before the flu season starts – which is April to September in the southern hemisphere, October to April in the northern hemisphere, and throughout the year in the tropics. For children, the nasal vaccine contains weakened live viruses while for adults the injected flu vaccine contains inactivated flu viruses. The vaccine cannot cause flu but it activates the immune system to initiate enough protection <a href="https://theconversation.com/sick-with-the-flu-heres-why-you-feel-so-bad-118395">in case the influenza infection strikes</a>.</p>
<p>It isn’t possible to predict the number of cases or the exact month when the flu season will hit in the UK. But flu generally circulates during winter and peaks in December and January. Though there have been alarming reports earlier in the year from Australia where more than 301,118 cases of flu were confirmed plus <a href="https://www.dailymail.co.uk/health/article-7546933/US-deadly-flu-season-Australias-sickened-272-000-killed-662.html">662 flu related deaths</a>. This is much higher than the <a href="https://www.immunisationcoalition.org.au/news-media/2019-influenza-statistics/?gclid=Cj0KCQjwvo_qBRDQARIsAE-bsH9KbVwAgrrKnjoRbO5LxDdHE6jW9FiAsCn2GILntms5Crfj75N836kaAsI7EALw_wcB">previous five-year average of around 110,000</a> in a season – and may be a sign of what is to come over the winter months in the UK. </p>
<h2>Asthma and the flu</h2>
<p>In healthy people flu usually clears up on its own within a week, but it can cause severe illness, complications and even death among <a href="https://www.nhs.uk/conditions/vaccinations/who-should-have-flu-vaccine/">vulnerable people</a> – this includes older people, pregnant women and people with an underlying health condition. These people are advised to have a flu vaccine each year.</p>
<p>Most asthmatics are entitled to a <a href="https://www.theguardian.com/society/2018/oct/17/asthmatics-must-get-flu-jab-before-winter-warn-doctors">free flu jab</a> on the NHS as they are classed as a vulnerable group – but not everyone takes up the offer. This is despite the fact that people with asthma – both adults and children – are more prone to <a href="https://www.cdc.gov/flu/highrisk/asthma.htm">develop pneumonia after the flu</a>. </p>
<p>The consequences of flu infection are much worse in asthmatics. This is in part because the <a href="https://www.cdc.gov/flu/highrisk/asthma.htm">flu virus causes inflammation</a> in the respiratory system – which not only triggers symptoms of asthma -— shortness of breath, wheezing and chest tightness —- but also makes those symptoms much more of an issue.</p>
<h2>Respiratory complications</h2>
<p>The reason why people with asthma show such a severe response to influenza is not fully understood. But the fact that the airways of people with asthma are different compared to the airways of healthy people, plays a big part.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/297875/original/file-20191021-56215-1orv7ju.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/297875/original/file-20191021-56215-1orv7ju.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/297875/original/file-20191021-56215-1orv7ju.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=294&fit=crop&dpr=1 600w, https://images.theconversation.com/files/297875/original/file-20191021-56215-1orv7ju.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=294&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/297875/original/file-20191021-56215-1orv7ju.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=294&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/297875/original/file-20191021-56215-1orv7ju.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=369&fit=crop&dpr=1 754w, https://images.theconversation.com/files/297875/original/file-20191021-56215-1orv7ju.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=369&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/297875/original/file-20191021-56215-1orv7ju.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=369&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Smooth muscles and basement membrane are thicker, there is more mucus secretion and epithelial loss in airways of people with asthma.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>In asthmatics, the airways have larger smooth muscles – which help to control the flow of air – and this can cause spasms and narrowing of the airways. Asthmatics also produce more mucus and have less epithelium. This a thin tissue lining on the outer layer of the airway surface that acts as the first protective barrier <a href="https://atlasofscience.org/what-do-we-know-and-what-can-we-do-about-asthma/">between inhaled pathogens</a> and the internal environment of the lung. This means there is less room for air to travel in the airways of asthmatics as they are narrower.</p>
<p>The combination of the flu and asthma symptoms is also highly problematic as the influenza virus <a href="https://jvi.asm.org/content/jvi/89/23/11935.full.pdf">directly target airway epithelial cells</a>. And the flu infection also leads to more mucus secretion which can block the airway of asthmatics. This can lead to increased risk of complications and exposes the lungs to severe, possibly even long-term, damage.</p>
<h2>Airways and asthma</h2>
<p><a href="https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-018-0851-7">Our recent research has also shown</a> that healthy people have “mechanisms” in their airway epithelium to protect it from damage by the flu virus. But in asthmatics, these protective measures against infection are weaker so the influenza virus can cause more damage to <a href="https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-018-0851-7">airway epithelium</a>. </p>
<p>For people with asthma then, it is highly recommended to take necessary precautions. Make sure you get the flu vaccination and follow good personal hygiene – such as <a href="https://theconversation.com/health-check-how-long-should-you-stay-away-when-you-have-a-cold-or-the-flu-98702">covering coughs and sneezes</a> and <a href="https://www.asthma.org.uk/advice/triggers/colds-and-flu/">washing your hands regularly</a>. And remember to repeat your flu vaccination every year because the protection from the vaccine decreases over time and the vaccine can change each year to cover the <a href="https://www.nhs.uk/conditions/vaccinations/flu-vaccine-questions-answers/">current virus strains</a>.</p>
<p>And if you do end up with the flu as an asthmatic, don’t panic, just make sure you see your doctor right away to check your symptoms and receive proper medications.</p><img src="https://counter.theconversation.com/content/121347/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fatemeh Moheimani received funding from the University of Newcastle, Australia (Early Career Researcher and
New Staff Grants); McDonald Jones Homes Group Philanthropy Grant - HMRI, Australia, and TSANZ/AstraZeneca Grant
in Aid for severe asthma research, Australia. The co-authors of original research manuscript received the National Health and Medical Research Council (NHMRC: APP 1064405), Australia to DK; and fellowship (APP1079187) to PH, Brawn Fellowship, Faculty of Health and Medicine to PH.
Fatemeh Moheimani is affiliated with Hunter Medical Research Institute (HMRI) and the National Horizons Centre at Teesside University. She is also a conjoint lecturer at the University of Newcastle, Australia.
</span></em></p>The consequences of flu infection are much worse in asthmatics, here’s why.Fatemeh Moheimani, Lecturer in Biomedical Science, Teesside UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1170532019-05-29T12:34:25Z2019-05-29T12:34:25ZThis year the flu came in two waves – here’s why<figure><img src="https://images.theconversation.com/files/276887/original/file-20190528-42571-xthzhf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">They're not perfect, but flu shots are still good to get.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Flu-Season/a1448982c7f4466e95d3fd4e136c007a/1/0">AP Photo/David Goldman</a></span></figcaption></figure><p>The just-ended 2018-2019 flu season was relatively mild compared to the last season, during which nearly 80,000 people in the U.S. died of flu-related illness, according to <a href="https://www.cdc.gov/flu/about/burden/2017-2018.htm">estimates by the U.S. Centers for Disease Control and Prevention</a>. </p>
<p><a href="https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm">This year’s death toll</a> is predicted to be about half, or, in the worst case, three-quarters of that number.</p>
<p>The 2018-2019 season has been unusual, though, because the <a href="https://www.cdc.gov/flu/weekly/index.htm">flu came in two waves</a>: one that peaked at the end of December, and a second that peaked in early March. The two peaks were caused by two different strains of the flu virus, and the protection given by vaccination early in the season may have waned by the time the second strain appeared.</p>
<p>Flu epidemics reoccur every year because of the way the virus is built and how it interacts with the human immune system. The viruses are highly changeable, acquiring genetic variations, called mutations, even within a single season. The new properties conferred by these mutations can allow the virus to evade the immune response elicited by the flu vaccine.</p>
<p>In addition, the immunity conveyed by a flu shot does not last from year to year. In fact, depending on the flu strain that is circulating, <a href="https://science.sciencemag.org/content/364/6437/224.long">immunity may not even last</a> through one flu season.</p>
<p>Here’s how it all added up over the flu season that has just drawn to a close.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/275494/original/file-20190520-69192-tfb8v3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/275494/original/file-20190520-69192-tfb8v3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/275494/original/file-20190520-69192-tfb8v3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=501&fit=crop&dpr=1 600w, https://images.theconversation.com/files/275494/original/file-20190520-69192-tfb8v3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=501&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/275494/original/file-20190520-69192-tfb8v3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=501&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/275494/original/file-20190520-69192-tfb8v3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=629&fit=crop&dpr=1 754w, https://images.theconversation.com/files/275494/original/file-20190520-69192-tfb8v3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=629&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/275494/original/file-20190520-69192-tfb8v3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=629&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Graphical representation of an influenza virus illustrating the proteins exposed on the surface.</span>
<span class="attribution"><a class="source" href="https://www.cdc.gov/flu/resource-center/freeresources/graphics/images.htm">Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Having flu once can protect from the same virus</h2>
<p>When you’re first exposed to the live flu virus, your immune system shifts into gear to try to fend off the invader. Specialized white blood cells, called B-cells, make antibodies that attack two proteins that poke off the surface of the virus, preventing them from doing their jobs. These viral surface proteins, called haemagglutinin (HA) and neuraminidase (NA), are necessary for the virus to survive.</p>
<p>Your immune response may not be fast enough to stop the virus from successfully invading your respiratory tract cells and causing flu symptoms. However, over the course of the infection different parts of the virus evoke an immune response that is more extensive and longer lasting.</p>
<p>Once the infection is over, special cells, called memory B-cells, lie dormant, waiting for a second invasion of the same virus. If they recognize the previously fought flu virus, they launch a <a href="https://doi.org/10.1038/s41577-019-0143-6">rapid immune response</a>.</p>
<p>Vaccines are designed to get your immune system ready to confront a virus without having to first be infected to learn about it. Every year, the World Health Organization <a href="https://www.who.int/influenza/vaccines/en/">predicts which flu strains will circulate</a> and vaccines are formulated with the anticipated strains.</p>
<p>Almost all current flu vaccines are made with killed virus. After injection, most of the antibodies made by the <a href="https://doi.org/10.1038/s41577-019-0143-6">immune system’s B-cells</a> are directed toward the “head” region of HA, the part that’s sticking furthest off the protein stalk from the surface of the virus. These antibodies prevent subsequent infection because the HA head is what makes first contact with the cells of the respiratory tract.</p>
<p>Because the dead viruses in the vaccine do not infect and grow, the wave of antibodies they induce is fairly short-lived and the vaccine <a href="https://doi.org/10.1016/j.coi.2019.02.007">is not great at creating memory cells</a>. The challenge to your immune system from the vaccine is much more limited than if it were facing a full-on onslaught of live viruses.</p>
<p>That short memory is one reason why you need to be vaccinated every season – even if the same virus is circulating, your immunity to it may be gone by the next year.</p>
<h2>Flu virus can change to outflank immune system</h2>
<p>The immune systems of all the people exposed to the flu virus are constantly attacking HA and, to a lesser degree, NA. This means that substrains of the flu virus with small changes in these proteins that allow them to evade the attack are more likely to survive – and so get passed on and become more common. This progression of small changes in the virus is called <a href="https://www.cdc.gov/flu/about/viruses/change.htm">antigenic drift</a>.</p>
<p>Flu viruses also can change more drastically by picking up genetic material from flu viruses in other animals, such as birds and pigs, a process called <a href="https://www.cdc.gov/flu/about/viruses/change.htm">antigenic shift</a>.</p>
<p>Antigenic drift produces the substrains that cause the yearly epidemics, whereas antigenic shift causes pandemics, such as the 2009 worldwide pandemic caused by the “<a href="https://www.cdc.gov/h1n1flu/information_h1n1_virus_qa.htm">swine flu</a>.”</p>
<p>Influenza A strains are identified by the versions of HA and NA that they carry; A(H1N1) and A(H3N2) are the strains that are circulating today. Exposure to one set of HA and NA proteins provides little protection when a virus carrying a different set comes along. This is the second reason why you need to be vaccinated every year – even if immunity conveyed by the vaccine lasts long enough, the viruses may have changed since the previous year.</p>
<p>Despite the shortcomings of the vaccines, public health officials still recommend getting that annual flu shot. Even if not perfectly matched, the antibodies the vaccine induces can give partial protection, making the <a href="https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm">flu less severe</a> than it otherwise would be.</p>
<h2>Two flu strains, peaking at different times</h2>
<p>At the start of the 2018-2019 flu season, the <a href="https://www.cdc.gov/flu/weekly/index.htm">dominant circulating strain of virus was A(H1N1)</a>, and the <a href="https://www.cdc.gov/mmwr/volumes/68/wr/mm6806a2.htm?s_cid=mm6806a2_w">flu vaccine was well matched to it</a>.</p>
<p>The more virulent strain, A(H3N2), was present at a low level until mid-January, when its incidence started sharply increasing. At the same time, the number of people with flu-like illness, which had been decreasing, started rising again. </p>
<p>By mid-February, A(H3N2) was the dominant flu strain circulating, and the number of <a href="https://www.cdc.gov/flu/weekly/index.htm">people with flu-like illness was at its peak</a>.</p>
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<p>The HA proteins of the many of the A(H3N2) viruses that appeared late in the season were significantly different from the HA of the virus that was used for the vaccine. There were <a href="https://www.cdc.gov/flu/weekly/weeklyarchives2018-2019/Week19.htm">several different substrains of A(H3N2) circulating</a>, and the vaccine was poorly matched to over half of them.</p>
<p>And remember, <a href="https://doi.org/10.1093/cid/ciw816">flu immunity steadily wanes after vaccination</a>. The effectiveness of the vaccine against A(H3N2) starts low, typically about 35%. So, by five months after vaccination, <a href="https://science.sciencemag.org/content/364/6437/224.long">it is essentially zero</a>. People vaccinated in September had little immunity by February to any of the circulating A(H3N2) substrains, even the one used in the vaccine.</p>
<p>These two factors – poor match of the vaccine to the late arising A(H3N2) viruses and waning immunity – account for the second wave of flu in the 2018-2019 season.</p>
<h2>Hoping for a one-and-done shot</h2>
<p>Scientists are trying to make a “universal vaccine” that would immunize against all, or most, flu strains and also give protection lasting more than one season. </p>
<p>Most strategies attempt to redirect the immune response away from the highly variable HA head region toward other <a href="https://doi.org/10.1093/infdis/jiy711">less variable parts of HA</a> or other <a href="https://doi.org/10.1080/14760584.2017.1379396">less mutable viral proteins</a>. Several of these prototypes are in <a href="https://www.asm.org/Articles/2019/April/Is-a-Universal-Influenza-Vaccine-on-the-Horizon">clinical trials</a>. </p>
<p>Not all of these proposed vaccines will prevent infection, but instead are designed to make an infection less severe. That may be the most important goal – not to prevent the flu, but to <a href="https://doi.org/10.1093/infdis/jiy728">stop it from killing people</a>.</p><img src="https://counter.theconversation.com/content/117053/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patricia L. Foster receives funding from the US Army Research Office. She is a member of the Union of Concerned Scientists and Concerned Scientists at Indiana University.</span></em></p>The 2018-2019 flu season was less deadly than the last. But the pattern of infection was unusual, thanks to the various strains circulating and the way flu shots work over time.Patricia L. Foster, Professor Emerita of Biology, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1050952018-10-23T10:42:41Z2018-10-23T10:42:41ZWhy did the flu kill 80,000 Americans last year?<figure><img src="https://images.theconversation.com/files/241730/original/file-20181022-105782-1x5js8k.jpg?ixlib=rb-1.1.0&rect=344%2C0%2C5009%2C3492&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An Atlanta hospital set up a mobile ER to deal with the large number of flu cases.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Flu-Season/f65dc500f98a425cbe2be0f1439099c8/2/0">AP Photo/David Goldman</a></span></figcaption></figure><p>The 2017-2018 flu season was <a href="https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm">historically severe</a>. Public health officials estimate that <a href="http://www.nfid.org/newsroom/news-conferences/2018-nfid-influenza-pneumococcal-news-conference/press-release.pdf">900,000 Americans were hospitalized and 80,000 died</a> from the flu and its complications. For comparison, the previous worst season from the past decade, 2010-2011, saw 56,000 deaths. In a <a href="https://www.cdc.gov/flu/about/disease/us_flu-related_deaths.htm">typical season, 30,000 Americans die</a>.</p>
<p>So why was the 2017-2018 season such a bad year for flu? There were two big factors.</p>
<p>First, one of the circulating strains of the influenza virus, A(H3N2), is particularly virulent, and vaccines targeting it are less effective than those aimed at other strains. In addition, most of the vaccine produced was mismatched to the circulating A(H3N2) subtype.</p>
<p>These problems reflect the special biology of the influenza virus and the methods by which vaccines are produced.</p>
<h2>Flu virus is a quick change artist</h2>
<p>Influenza is not a single, static virus. There are three species – A, B and C – that can infect people. A is the most serious and C is rare, producing only mild symptoms. Flu is further divided into various subtypes and strains, <a href="https://doi.org/10.1016/j.vaccine.2008.07.039">based on the viral properties</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/241734/original/file-20181022-105782-1rlcp91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/241734/original/file-20181022-105782-1rlcp91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/241734/original/file-20181022-105782-1rlcp91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=395&fit=crop&dpr=1 600w, https://images.theconversation.com/files/241734/original/file-20181022-105782-1rlcp91.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=395&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/241734/original/file-20181022-105782-1rlcp91.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=395&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/241734/original/file-20181022-105782-1rlcp91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=497&fit=crop&dpr=1 754w, https://images.theconversation.com/files/241734/original/file-20181022-105782-1rlcp91.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=497&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/241734/original/file-20181022-105782-1rlcp91.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=497&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cartoon depiction of an influenza virus structure. Different strains are named after their versions of the haemagglutinin and neuraminidase proteins, as in H1N1 ‘swine flu.’</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/structure-influenza-virus-infographics-vector-illustration-542924464?src=ixiW0w-59I3I17RpN4L3wQ-1-12">Timonina/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Viruses consist of protein packages surrounding the viral genome, which, in the influenza virus, consists of RNA divided into eight separate segments. The influenza virus is enveloped by a membrane layer derived from the host cell. Sticking through this membrane are spikes made up of the proteins haemagglutinin (HA) and neuraminidase (NA), both of which are required for the virus to successfully cause an infection.</p>
<p>Your immune system reacts first to these two proteins. Their properties determine the H and N designations of various viral strains – for instance, the <a href="https://www.cdc.gov/h1n1flu/">H1N1 “swine flu”</a> that swept the globe in 2009.</p>
<p>Both HA and NA proteins are constantly changing. The process that copies the viral RNA genome is inherently sloppy, plus these two proteins are under strong pressure to evolve so they can evade attack by the immune system. This evolution of the HA and NA proteins, <a href="https://www.cdc.gov/flu/about/viruses/change.htm">called antigenic drift</a>, prevents people from developing lasting immunity to the virus. Although the immune system may be prepared to shutdown previously encountered strains, even slight changes can require the development of a completely new immune response before the infected person becomes resistant. Thus we have seasonal flu outbreaks.</p>
<p>In addition, <a href="https://theconversation.com/influenzas-wild-origins-in-the-animals-around-us-91058">various subtypes of influenza A infect animals</a>, the most important of which, for humans, are domestic birds and pigs. If an animal is simultaneously infected with two different subtypes, the segments of their genomes can be scrambled together. Any resulting virus may have new properties, to which humans may have little or no immune defense. This process, <a href="https://www.cdc.gov/flu/about/viruses/change.htm">called antigenic shift</a>, is responsible for the <a href="https://doi.org/10.3201/eid1201.051254">major pandemics that have swept the world</a> in the last century.</p>
<h2>Forecasting flu, producing vaccine</h2>
<p>Against this background of antigenic change, every year the World Health Organization predicts <a href="https://www.who.int/influenza/vaccines/virus/recommendations/2018_19_north/en/">which strains of flu virus will be circulating</a> during the next flu season, and vaccines are formulated based on this information.</p>
<p><iframe id="ajXan" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/ajXan/2/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>In 2017-2018 the vaccine was directed against specific subtypes of A(H1N1), A(H3N2) and B. The Centers for Disease Control and Prevention estimates that this <a href="https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm">vaccine was 40 percent effective</a> in preventing influenza overall. But, significantly, it was only 25 percent effective against the especially dangerous A(H3N2) strain. This mismatch probably reflects the way most of the vaccines are produced.</p>
<p>The common way of producing influenza vaccine starts by <a href="https://doi.org/10.3390/vaccines6020019">growing the virus in fertilized chicken eggs</a>. After several days, the viruses are harvested, purified and inactivated, leaving the surface proteins, HA and NA, intact. But, when the virus is grown in eggs, individual viruses with changes in the HA protein that increase its ability to bind to chicken cells can grow better and thus become more common.</p>
<p>When people receive vaccines produced from these egg-adapted viruses, their immune system learns to target the egg-influenced HA proteins and may not react to the HA proteins <a href="https://doi.org/10.1056/NEJMp1714916">on the viruses actually circulating in humans</a>. Thus, the virus used to produce much of the 2017-2018 vaccine provoked an immune response that did not fully protect against the A(H3N2) virus circulating in the population – although it <a href="https://doi.org/10.1016/j.vaccine.2018.07.028">may have lessened the severity of the flu</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/241731/original/file-20181022-105748-72zkeq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/241731/original/file-20181022-105748-72zkeq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/241731/original/file-20181022-105748-72zkeq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=488&fit=crop&dpr=1 600w, https://images.theconversation.com/files/241731/original/file-20181022-105748-72zkeq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=488&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/241731/original/file-20181022-105748-72zkeq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=488&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/241731/original/file-20181022-105748-72zkeq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=614&fit=crop&dpr=1 754w, https://images.theconversation.com/files/241731/original/file-20181022-105748-72zkeq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=614&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/241731/original/file-20181022-105748-72zkeq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=614&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Influenza vaccine has been produced in chicken eggs for decades.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Watchf-AP-A-IN-USA-APHS235246-Mmed-amp-Surg-/b8663fde84aa410ab8c302755c6a0777/5/0">AP Photo</a></span>
</figcaption>
</figure>
<h2>Small improvements and a universal vaccine</h2>
<p>Scientists are on the hunt for a better way to protect the world’s population from influenza.</p>
<p>Two new vaccines that do not use egg-grown viruses are currently available. One, a <a href="https://www.statnews.com/2018/03/09/cell-culture-flu-vaccine-flucelvax/">vaccine made from viruses grown in mammalian cells</a>, proved in preliminary studies to be only 20 percent more effective against A(H3N2) than egg-produced vaccine. The other, <a href="https://www.cdc.gov/flu/protect/vaccine/qa_flublok-vaccine.htm">a “recombinant” vaccine</a> consisting of only the HA proteins, is <a href="https://doi.org/10.1177/2051013615595595">produced in insect cells</a>, and its effectiveness is still being evaluated.</p>
<p>The ideal solution is <a href="https://www.scientificamerican.com/article/we-need-a-universal-flu-vaccine-before-the-next-pandemic-strikes/">a “universal” vaccine</a> that would protect against all influenza viruses, no matter how the strains mutate and evolve. One effort relies on the fact that flu’s HA protein “stalk” is less variable than the “head” that interacts with the host cell surface; but <a href="https://doi.org/10.3389/fimmu.2018.01479">vaccines made from a cocktail of HA protein “stalks”</a> have proved disappointing so far. A vaccine composed of <a href="https://clinicaltrials.gov/ct2/show/NCT03277456">two proteins internal to the virus</a>, M1 and NP, which are much less variable than surface-exposed proteins, is in clinical trials, as is another vaccine made up of a proprietary mixture of <a href="https://clinicaltrials.gov/ct2/show/NCT03450915">pieces of viral proteins</a>. These vaccines are designed to stimulate the “memory” immune cells that persist after an infection, possibly providing lasting immunity.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/241732/original/file-20181022-105751-13ehbb1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/241732/original/file-20181022-105751-13ehbb1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/241732/original/file-20181022-105751-13ehbb1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=389&fit=crop&dpr=1 600w, https://images.theconversation.com/files/241732/original/file-20181022-105751-13ehbb1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=389&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/241732/original/file-20181022-105751-13ehbb1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=389&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/241732/original/file-20181022-105751-13ehbb1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=489&fit=crop&dpr=1 754w, https://images.theconversation.com/files/241732/original/file-20181022-105751-13ehbb1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=489&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/241732/original/file-20181022-105751-13ehbb1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=489&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This year’s vaccine looks like it will be a better match.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/California-Flu-Season/bc91acbda14d47d8a7f47107d56d3c71/4/0">AP Photo/Jeff Chiu</a></span>
</figcaption>
</figure>
<h2>Will the 2018-2019 flu season be as bad?</h2>
<p>Based mainly on the recent flu season in South America, the <a href="http://www.who.int/influenza/vaccines/virus/recommendations/201802_recommendation.pdf">World Health Organization recommended</a> changing the A(H3N2) subtype in the vaccine to one that better matches last year’s circulating A(H3N2). They also recommended changing the B subtype to one that appeared in the U.S. late in the 2017-2018 season and became increasingly common elsewhere. The WHO anticipated that the circulating A(H1N1) subtype will be the same as last year and so no change was necessary on that front. So, although the same strains will most likely be circulating, epidemiologists expect the vaccines to provide better protection. </p>
<p>The CDC recommends that everyone 6 months and older <a href="https://www.cdc.gov/flu/prevent/vaccinations.htm">get a flu shot every year</a>, but, typically, <a href="https://www.cdc.gov/flu/fluvaxview/interactive.htm">fewer than half of Americans do so</a>. Flu and its complications can be life-threatening, particularly for the young, the old and the otherwise debilitated. Most years the vaccine is well matched to the circulating virus strain, and even a poorly matched vaccine offers protection. Plus, wide-spread vaccination stops the virus from spreading and protects the vulnerable.</p>
<p>The first flu death of the 2018-2019 season has already occurred – a <a href="https://www.nytimes.com/2018/10/16/health/child-flu-death-florida.html">healthy but unvaccinated child died</a> in Florida – affirming the importance of getting the flu shot.</p><img src="https://counter.theconversation.com/content/105095/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patricia L. Foster receives funding from the US Army Research Office. She is affiliated with Union of Concerned Scientists and Concerned Scientists at Indiana University. </span></em></p>Part of the problem was a mismatch between the influenza strains circulating and the vaccine available. Here’s how annual flu shots are formulated.Patricia L. Foster, Professor Emerita of Biology, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/910582018-03-09T11:39:47Z2018-03-09T11:39:47ZInfluenza’s wild origins in the animals around us<figure><img src="https://images.theconversation.com/files/209607/original/file-20180308-30954-1affwjl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People and animals live side by side – and can have pathogens in common.</span> <span class="attribution"><span class="source">Nichola Hill</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>In the early 20th century, the <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4829a1.htm">leading cause of death</a> was infectious disease. Epidemics erupted with little warning, seemingly out of the blue. When the “Great Influenza” struck in 1918, it <a href="https://www.penguinrandomhouse.com/books/288950/the-great-influenza-by-john-m-barry/9780143036494">killed thousands of people a week</a> in American cities and spread like wildfire around the globe. My great aunt, still a teenager, and living in the San Francisco area, was one of its estimated <a href="https://dx.doi.org/10.3201/eid1201.050979">50 to 100 million victims worldwide</a>.</p>
<p>Neither public health authorities nor medical researchers understood that it was a virus that caused the 1918 pandemic – most of the world at that time didn’t even know what a virus was. A century later, <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4829a1.htm">death due to infection is much less common</a>, thanks to public health efforts and improved medical technology and expertise. <a href="http://www.berkeleywellness.com/healthy-community/health-care-policy/article/cdcs-top-10-public-health-achievements-20th-century">Once common diseases are now rare</a>. Nonetheless, infectious disease specialists like me still fear the emergence of viral diseases that we will not be able to control, including influenza.</p>
<p><a href="https://runstadlerlab.mit.edu/">My laboratory</a>, along with others around the world, is working to understand how and why new influenza viruses may grip us again. To do so, we need to go far beyond human hospitals and into the wild, where viruses persist in animal populations. As <a href="https://www.nature.com/scitable/knowledge/library/disease-ecology-15947677">disease ecologists</a>, we aim to understand the dynamics of pathogens in the environment and their interactions with hosts. By understanding more about what’s happening with viruses in animals, we believe we can be better prepared to evaluate, predict and respond if an infection spills over to humans, making people sick.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/209334/original/file-20180307-146650-1g83a4m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209334/original/file-20180307-146650-1g83a4m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/209334/original/file-20180307-146650-1g83a4m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=465&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209334/original/file-20180307-146650-1g83a4m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=465&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209334/original/file-20180307-146650-1g83a4m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=465&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209334/original/file-20180307-146650-1g83a4m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=584&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209334/original/file-20180307-146650-1g83a4m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=584&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209334/original/file-20180307-146650-1g83a4m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=584&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Tens of millions died, but no one knew a virus was to blame.</span>
<span class="attribution"><a class="source" href="http://resource.nlm.nih.gov/101399244">U.S. National Library of Medicine</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
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<h2>Identifying the invisible, infectious virus</h2>
<p>Until well into the 1930s, the <a href="http://www.history.com/news/ask-history/why-was-it-called-the-spanish-flu">“Spanish flu”</a> was mistakenly thought to be a bacterial infection, with <em>Haemophilus influenzae</em> commonly blamed. This bacterium is a pathogen in its own right and may have contributed heavily to the 1918 pandemic’s death toll – but it was a secondary infection in many of the severe cases, not the original cause of victims’ illnesses.</p>
<p>Researchers had only identified viral particles for the first time less than 30 years before the height of the flu pandemic and the fledgling field of virology was just beginning to identify them as causes of disease in plants and animals. Scientists were only first able to visualize a virus, the tobacco mosaic virus, after the 1931 invention of the electron microscope. Though the technology, knowledge and pace of research was different early in the 20th century, why did the discovery of influenza virus take so long? </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/209348/original/file-20180307-146666-1bkumam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209348/original/file-20180307-146666-1bkumam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/209348/original/file-20180307-146666-1bkumam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=637&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209348/original/file-20180307-146666-1bkumam.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=637&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209348/original/file-20180307-146666-1bkumam.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=637&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209348/original/file-20180307-146666-1bkumam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=801&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209348/original/file-20180307-146666-1bkumam.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=801&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209348/original/file-20180307-146666-1bkumam.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=801&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 transmission electron microscopic image of recreated 1918 influenza viral particles.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/sanofi-pasteur/34028429785">CDC/Dr. Terrence Tumpey</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
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<p>The answer, it seems, lay at least in part in people’s naiveté about the relationship between animals, the environment and human disease. In 1918, veterinarian J.S. Koen <a href="http://www.medicalecology.org/diseases/influenza/influenza.htm">noted a very similar disease to influenza in pigs</a>. Yet, it wasn’t until 1931 that researcher Richard Shope identified a filterable agent, smaller than bacteria, as the cause of the disease in pigs and demonstrated the transmission of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391305/">an influenza virus</a>. That work spurred the description of human influenza virus in 1933.</p>
<p>The tools of molecular biology, including <a href="https://www.yourgenome.org/stories/what-is-dna-sequencing">nucleic acid sequencing</a>, developed through the latter half of the 20th century, finally helped open the vault on the origins of the 1918 pandemic. In 2005, through a combination of sleuthing and sequencing of the viral genome, <a href="https://scholar.google.com/citations?user=pksBzvYAAAAJ&hl=en&oi=ao">Jeffrey Taubenberger</a> and a team of researchers pieced together the <a href="https://doi.org/10.1126/science.1119392">genetic sequence of the deadly 1918 virus</a>, using viruses collected from the corpses of soldiers and other bodies preserved in the Arctic permafrost who died during the pandemic.</p>
<p>They were able to connect the origins and evolution of the 1918 pandemic with viruses that circulate in other animals, particularly those from birds and the pigs examined by Dr. Koen. Just as seen in more recent outbreaks of new influenza viruses, the 1918 pandemic traced its origins to virus strains circulating in nature.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/209530/original/file-20180308-30972-k3j39x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209530/original/file-20180308-30972-k3j39x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/209530/original/file-20180308-30972-k3j39x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209530/original/file-20180308-30972-k3j39x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209530/original/file-20180308-30972-k3j39x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209530/original/file-20180308-30972-k3j39x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209530/original/file-20180308-30972-k3j39x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209530/original/file-20180308-30972-k3j39x.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"></a>
<figcaption>
<span class="caption">Disease ecologists now know that waterfowl can be a reservoir for influenza virus, and conduct surveillance on wild birds.</span>
<span class="attribution"><span class="source">Paige Gingrich</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Natural world a reservoir for human disease</h2>
<p>The critical insight that led to the work reconstructing the 1918 virus had come in the 1970s. Led by the determination of virologist Rob Webster, researchers realized that <a href="http://mmbr.asm.org/content/56/1/152.short">influenza viruses are rampant in the natural world</a>, particularly in waterfowl. In birds and possibly other animals, influenza viruses are able to replicate and transmit to new hosts without causing any severe disease. On rare occasions, given the right circumstance, this new host is a different species. This cycle, common in many pathogens, is an important part of how virus is maintained in nature and explains how animals can be a reservoir for novel influenza viruses that can cause human illnesses.</p>
<p>As researchers have sequenced the influenza viruses found in ducks and other birds, as well as people, swine and other animals, a picture of viral ecology based in nature has come into focus. Birds serve as a reservoir for a vast diversity of influenza viruses to which all the major human pandemics <a href="https://www.cdc.gov/flu/pandemic-resources/basics/past-pandemics.html">trace their origin</a>. People were largely unaware that at the same time as the 1918 flu pandemic, pigs were sick with the disease and influenza viruses were also causing ongoing fowl plague epidemics. Exactly how and where the 1918 virus <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC340389/">entered the human population</a> remains controversial. But the realization that influenza virus happily exists in a wild animal reservoir has influenced the way scientists study flu – and moreover, emerging disease of any sort.</p>
<p>This understanding is also part of what underlies the One Health movement – the concept that the health of humans is entwined with the health of animals and of the environment. The <a href="http://www.onehealthinitiative.com/index.php">One Health</a> and <a href="https://isemph.org/">Evolutionary Medicine</a> initiatives are forging collaborations between medical doctors, veterinarians, ecologists, environmental researchers and those in many other fields to describe the connections among environmental change, animals and human health.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/209609/original/file-20180308-30975-16qf7e2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209609/original/file-20180308-30975-16qf7e2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/209609/original/file-20180308-30975-16qf7e2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209609/original/file-20180308-30975-16qf7e2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209609/original/file-20180308-30975-16qf7e2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209609/original/file-20180308-30975-16qf7e2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209609/original/file-20180308-30975-16qf7e2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209609/original/file-20180308-30975-16qf7e2.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"></a>
<figcaption>
<span class="caption">Understanding virus ecology means figuring out what strains are circulating and how new strains are created in the wild.</span>
<span class="attribution"><span class="source">Nichola Hill</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Watching the wild world to protect human health</h2>
<p>We now know that a full <a href="https://www.cdc.gov/ncezid/">60 percent of human infectious diseases are spread from animals</a>. In the past 20 years, that awareness has resulted in stronger efforts at <a href="http://www.who.int/influenza/human_animal_interface/en/">influenza surveillance worldwide</a> and the identification of several other influenza viruses that threaten public health. In my lab’s work, we endeavor to describe the ecology and natural history of influenza virus in animals to understand how new viruses arise and what the risk is of spillover into new hosts where they may cause disease.</p>
<p>For instance, human activity – such as the existence of open landfills, habitat destruction or farming practices – can attract or force animals to crowd into spaces they normally may not. When interactions between species and the environment are disrupted in this way, how does it affect the circulation, evolution and movement of influenza viruses or other pathogens that those animals host? Changes in the ecology of pathogens in the wild are what most frequently leads to spillover into human populations and disease outbreak. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/209531/original/file-20180308-30983-1et9gln.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209531/original/file-20180308-30983-1et9gln.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/209531/original/file-20180308-30983-1et9gln.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209531/original/file-20180308-30983-1et9gln.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209531/original/file-20180308-30983-1et9gln.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209531/original/file-20180308-30983-1et9gln.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209531/original/file-20180308-30983-1et9gln.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209531/original/file-20180308-30983-1et9gln.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"></a>
<figcaption>
<span class="caption">The author and colleagues draw samples from wild seals in New England.</span>
<span class="attribution"><span class="source">Yvonne Vaillancourt, obtained under NMFS #17670</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
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<p>Following an epidemic of seal deaths in 2011 in New England, <a href="https://www.nefsc.noaa.gov/press_release/pr2016/scispot/ss1602/">our broad group of collaborators</a> has spent cold winter days sampling seals, where we’ve discovered evidence of persistent circulating influenza viruses. These results are leading us to explore how influenza is affecting the seals, but also what the impact of a rapidly expanding seal population will be on the virus. If seals are a mammalian reservoir more commonly infected than we knew, their populations may affect influenza disease ecology. </p>
<p>Surveillance and research work like that on influenza and its animal hosts has led to more aggressive efforts to stamp out emerging infections before they become human pandemics. It gives biomedical researchers a head start on characterizing possible pandemic viruses to understand their potential impact. And public health workers gain new insights on prevention and control of infection.</p>
<p>That information may be crucial in identifying and containing the next pandemic virus. The One Health community’s experience with influenza has informed how scientists try to understand and prevent the spread of other diseases, including <a href="https://evolution.berkeley.edu/evolibrary/news/060101_batsars">SARS</a>, <a href="https://www.cdc.gov/ncezid/stories-features/global-stories/ebola-reservoir-study.html">Ebola</a> and <a href="http://www.sciencemag.org/news/2017/08/zika-has-all-disappeared-americas-why">Zika</a>. Researchers were quick to chase after the animal source of SARS and are still hard at work to identify reservoir hosts and understand the disease ecology of the Zika and Ebola viruses.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/209344/original/file-20180307-146671-1rvnlcj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209344/original/file-20180307-146671-1rvnlcj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/209344/original/file-20180307-146671-1rvnlcj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209344/original/file-20180307-146671-1rvnlcj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209344/original/file-20180307-146671-1rvnlcj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209344/original/file-20180307-146671-1rvnlcj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209344/original/file-20180307-146671-1rvnlcj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209344/original/file-20180307-146671-1rvnlcj.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"></a>
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<span class="caption">Sampling birds, as at this market in Bangkok, lets researchers keep track of viruses circulating and mixing in human environments.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/usaidasia/16191808288">Richard Nyberg, USAID</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
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<p>Over one hundred years after the “Great Influenza,” there’s still much to learn to lessen the risk of a repeat of 1918. In the last 10 years, thanks to the efforts of many researchers worldwide, including a <a href="http://www.niaidceirs.org">renewed effort funded by the U.S. National Institutes of Health</a>, the pace of sequencing influenza viruses has leapt forward. Scientists are beginning to understand the true diversity of influenza virus, not only in birds, but in other animals as well.</p>
<p>Efforts at <a href="https://theconversation.com/influenza-the-search-for-a-universal-vaccine-90908">producing a universal vaccine</a> to prevent influenza infection in humans show promise. But the ability to test those vaccines and to prepare for and predict emerging strains will not be complete without a strong understanding of the origin, movement and risk of viruses circulating in the animals and environment around us. With better understanding of these ecological connections coming from continued research, we hope we can be better prepared for the next pandemic.</p><img src="https://counter.theconversation.com/content/91058/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Runstadler receives funding from National Institutes of Health (HHSN272201400008C)</span></em></p>No one then knew a virus caused the 1918 flu pandemic, much less that animals can be a reservoir for human illnesses. Now virus ecology research and surveillance are key for public health efforts.Jonathan Runstadler, Professor of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/909082018-02-15T11:37:52Z2018-02-15T11:37:52ZInfluenza: The search for a universal vaccine<figure><img src="https://images.theconversation.com/files/206388/original/file-20180214-174959-1ookhri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Could the yearly flu shot become a thing of the past?</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/HealthBeat-Flu-Shots-Things-to-Know/1785b0ccc496487f9768ae2315387e89/6/0">AP Photo/Darron Cummings, File</a></span></figcaption></figure><p>The current 2017-18 flu season is a bad one. <a href="https://www.cdc.gov/media/releases/2018/t0202-flu-update-activity.html">Hospitalization rates are now</a> higher than in recent years at the same point, and <a href="https://www.nytimes.com/2018/02/02/health/flu-symptoms-virus-hospital.html">infection rates are still rising</a>. The best line of defense is the seasonal influenza vaccine. But <a href="https://doi.org/10.1073/pnas.1712377114">H3N2 viruses</a>, like the one that’s infecting many people this year, are particularly hard to defend against, and this year’s shot <a href="https://www.statnews.com/2018/02/01/flu-vaccine-protection-h3n2/">isn’t very protective</a> against H3N2.</p>
<p>Producing an effective annual flu shot relies on accurately predicting which flu strains are most likely to infect the population in any given season. It requires the coordination of multiple health centers around the globe as the virus travels from region to region. Once epidemiologists settle on target flu strains, vaccine production shifts into high gear; it takes <a href="https://www.cdc.gov/flu/about/season/vaccine-selection.htm">at least six months</a> to generate the <a href="https://www.cdc.gov/flu/professionals/vaccination/vaccinesupply.htm">more than 140 million doses</a> necessary for the American population.</p>
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<p>Incorrect or incomplete epidemiological forecasting can have major consequences. In 2009, while manufacturers were preparing vaccines against the forecasted strains, an <a href="https://www.cdc.gov/h1n1flu/cdcresponse.htm#A_Pandemic_Is_Declared">unanticipated H1N1 influenza virus</a> emerged. The prepared seasonal vaccine didn’t protect against this unanticipated virus, causing worldwide panic and over 18,000 confirmed deaths. This was likely only a fraction of the true number of deaths, <a href="http://dx.doi.org/10.1016/S1473-3099(12)70121-4">estimated to exceed 150,000</a>. Better late than never, a <a href="https://www.cdc.gov/flu/pastseasons/0910season.htm">vaccine was eventually produced against the emergent H1N1</a>, requiring a second flu shot that year.</p>
<p>Given that influenza has caused the majority of <a href="https://www.cdc.gov/flu/pandemic-resources/basics/past-pandemics.html">pandemics over the past 100 years</a> – including the 1918 flu that <a href="http://doi.org/10.1353/bhm.2002.0022">resulted in as many as 50 million deaths</a> – we’re left with the question: Can scientists produce a “universal” vaccine? An ideal version would be capable of protecting against diverse strains of influenza and wouldn’t require a yearly shot for you.</p>
<h2>Vaccines prime the immune system to fight</h2>
<p>By the 18th century, and arguably much earlier in history, it was commonly known that a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/">survivor of smallpox would not come down with it again</a> upon subsequent exposure. Somehow, infection conferred immunity against the disease. In fact, people recognized that milkmaids who came into contact with cowpox-ridden cattle would similarly be protected from smallpox.</p>
<p>In the late 1700s, farmer <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/">Benjamin Jesty inoculated his family with cowpox</a>, effectively immunizing them against smallpox. Physician <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC495097/">Edward Jenner then catapulted humanity into a new age of immunology</a> when he lent scientific credence to the procedure.</p>
<p>So if one inoculation of cowpox or one exposure to (and survival of) smallpox confers a decade’s worth or even lifelong immunity, why are individuals encouraged to receive the flu vaccine every year? </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=471&fit=crop&dpr=1 600w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=471&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=471&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=592&fit=crop&dpr=1 754w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=592&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=592&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An artist’s rendition of the anatomy of a virus.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/30738089686">Anna Tanczos/Wellcome Images</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
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<p>The answer lies in how quickly the influenza virus’s anatomy changes. Each virus consists of a roughly spherical membrane encapsulating constantly mutating genetic material. This membrane is peppered with two types of “spikes”: hemagglutinin, or HA, and neuraminidase, or NA, each made up of a stem and a head. HA and NA help the virus with infection by binding to host cells. They mediate the entry of the virus into the cell and, once it replicates, the eventual exit.</p>
<p>Once a doctor injects a vaccine, an individual’s immune system gets to work by making antibodies that recognize, for example, the hemagglutinin it contains. The next time that hemagglutinin shows up – such as in the form of the virus strains the vaccine mimicked – the body’s immune cells recognize them and fight them off, preventing infection.</p>
<p>For vaccine developers, one frustrating characteristic about influenza’s mutating genome is how rapidly HA and NA change. These constant alterations are what send them back to the drawing board for new vaccines every flu season.</p>
<h2>Different methods to design a vaccine</h2>
<p>The smallpox vaccine was one of the earliest to use the “empirical paradigm” of vaccinology – the same strategy we largely use today. It relies on a trial-and-error approach to mimic the immunity induced by natural infection.</p>
<p>In other words, vaccine developers believe the body will react to something in the inoculation. But they don’t focus on which specific patch of the virus is causing that immune response. It doesn’t really matter if it’s a reaction to a small patch of HA that many strains share, for instance. When using an entire virus as starting material, it’s possible to get many different antibodies recognizing many different parts of the virus used in the vaccine.</p>
<p>The seasonal flu shot generally fits into this empirical approach. Each year, epidemiologists forecast which flu strains are most likely to infect populations, typically settling on three or four. Researchers then attenuate or inactivate these strains so they can act as the mimics in that year’s influenza vaccine without giving recipients the flu. The hope is that an individual’s immune system will respond to the vaccine by creating antibodies that target these strains; then when he or she comes into contact with the flu, the antibodies will be waiting to neutralize those strains. </p>
<p>But there’s a different way to design a vaccine. It’s <a href="https://doi.org/10.1371/journal.ppat.1003001">called rational design</a> and represents a potentially game-changing paradigm shift in vaccinology. </p>
<p>The goal is to design some molecule – or immunogen – that can trigger the production of effective antibodies without requiring exposure to the virus. Relative to current vaccines, the engineered immunogen may even allow for more specific responses, meaning the immune response targets particular regions of the virus. There’s the possibility of greater breadth, too, meaning it could target multiple strains or even related viruses.</p>
<p>This strategy works to target specific epitopes, or patches of the virus. Since antibodies work by recognizing structures, the designers want to emphasize to the immune system the structural properties of the immunogens they’ve created. Then researchers can try to design candidate vaccines with those structures in hopes they’ll provoke the immune system to produce relevant antibodies. This path might let them assemble a vaccine that elicits a more effective and efficient immune response than would be possible with the traditional trial-and-error method.</p>
<p>Promising headway has been made in <a href="http://doi.org/10.1038/nature12966">vaccine design for respiratory syncytial virus</a> using this new rational paradigm, but efforts are still underway to use this general approach for influenza.</p>
<h2>Toward a universal flu vaccine</h2>
<p>In recent years, researchers have isolated a number of potent, infleunza-neutralizing antibodies produced in our bodies. While the antibody response to influenza is <a href="http://doi.org/10.1128/JVI.03562-13">primarily directed at the head of the HA spike</a>, several have been found that <a href="http://doi.org/10.1038/nsmb.1566">target HA’s stem</a>. Since the stem is more constant across viral strains than the head, this could be flu’s Achilles’ heel, and antibodies that fix on this region may be a good target for vaccine design.</p>
<p>Researchers are pursuing a number of approaches that could cause the body to produce these antibodies of interest before becoming infected. In one strategy, scientists attached lab-made copies of hemagglutanin stems to a spherical protein nanoparticle. The resultant structure isn’t a virus and doesn’t even contain any viral genetic material. But it looks a lot like a virus to the body’s immune system, and so <a href="https://retrovirology.biomedcentral.com/articles/10.1186/s12977-015-0210-4">elicits a good antibody response</a>. And, because only the stem is attached to the nanoparticle, the immune system can focus the antibody response on these regions which are more similar from strain to strain than the head. This general approach has seen success both <a href="https://doi.org/10.1038/s41467-017-02725-4">in mice</a> <a href="https://doi.org/10.1038/nm.3927">and ferrets</a>, but further testing is required before it can be tried in people.</p>
<p>With current technology, there may never be a “one and done” flu shot. And epidemiological surveillance will always be necessary. However, it is not inconceivable that we can move from a once-per-year model to a once-every-10-years approach, and the field has been making huge strides to achieve this.</p>
<p><em>This is an updated version of an article <a href="https://theconversation.com/influenza-the-search-for-a-universal-vaccine-68947">originally published on Jan. 11, 2017</a>.</em></p><img src="https://counter.theconversation.com/content/90908/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Setliff's institution receives funding from the NIH and Ian is affiliated with the Vanderbilt Vaccine Center.</span></em></p><p class="fine-print"><em><span>Amyn Murji receives funding from the NIH and is affiliated with the Vanderbilt Vaccine Center.</span></em></p>Flu virus mutates so quickly that one year’s vaccine won’t work on the next year’s common strains. But rational design – a new way to create vaccines – might pave the way for more lasting solutions.Ian Setliff, Ph.D. Candidate in Chemical & Physical Biology, Vanderbilt Vaccine Center, Vanderbilt UniversityAmyn Murji, Ph.D. Student in Microbiology and Immunology, Vanderbilt Vaccine Center, Vanderbilt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/899602018-01-11T19:36:47Z2018-01-11T19:36:47Z‘Aussie flu’? We can’t be sure where flu originates, and that doesn’t really matter anyway<p>Britain’s media have made much of the “<a href="https://www.thesun.co.uk/news/5295083/aussie-flu-uk-maps-news-latest-2018/">Aussie flu</a>” sweeping across the northern hemisphere, but is there evidence the land Down Under is to blame? </p>
<p>There are a few things we know. Flu viruses circulate all year around, all over the world and they are constantly <a href="https://elifesciences.org/articles/01914#fig1">evolving</a> through <a href="https://theconversation.com/how-we-change-the-organisms-that-infect-us-74625">mutation</a>. This means even viruses of the same subtype can be slightly different, and so vaccines against the subtype won’t necessarily work on newly mutated forms.</p>
<p>Flu viruses are also shared around the globe thanks to air travel. In temperate climates we see a short period in winter when flu cases leap up – a flu epidemic – that occurs every year.</p>
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Read more:
<a href="https://theconversation.com/heres-why-the-2017-flu-season-was-so-bad-86605">Here's why the 2017 flu season was so bad</a>
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<p>Not all flu cases in Britain, or anywhere else, are being caused by just one flu virus. Multiple flu viruses circulate each year and are broadly grouped into two types: A and B.</p>
<p>Influenza B viruses form two main groups, while the influenza A viruses are more variable. The most common influenza A strains are A/H3N2 and A/H1N1 (which may sound familiar as it was the strain that caused the 2009 “swine flu” epidemic).</p>
<p>The main influenza A subtype in the 2017/18 British season is the same as it was in the Australian season; the most rapidly mutating flu virus subtype, A/H3N2. </p>
<p>There is also some A/H1N1 and both forms of flu B virus getting around. </p>
<p>Tropical East-Southeast Asia, where flu season is more constant (as they don’t have a “winter” for it to peak), is often a global <a href="https://www.nature.com/articles/nature14460">source</a> for new seasonal flu A variants. </p>
<p>The <a href="https://www.gov.uk/government/statistics/weekly-national-flu-reports">UK flu report</a> shows H3N2 is the main virus being detected, but intensive care admissions – a marker of serious disease – show flu B is having a big impact too, in all age groups but especially children.</p>
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<strong>
Read more:
<a href="https://theconversation.com/ive-always-wondered-why-is-the-flu-virus-so-much-worse-than-the-common-cold-virus-83495">I've always wondered: why is the flu virus so much worse than the common cold virus?</a>
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<a href="https://images.theconversation.com/files/201584/original/file-20180111-46709-1d2tgxr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/201584/original/file-20180111-46709-1d2tgxr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/201584/original/file-20180111-46709-1d2tgxr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/201584/original/file-20180111-46709-1d2tgxr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/201584/original/file-20180111-46709-1d2tgxr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/201584/original/file-20180111-46709-1d2tgxr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/201584/original/file-20180111-46709-1d2tgxr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/201584/original/file-20180111-46709-1d2tgxr.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">Flu can travel between countries via air travel.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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<p>There is no easy way to prove the viruses in Britain originated in Australia. Detailed genetic sequencing and detective work could help, but that work hasn’t been done and it’s an academic question anyway. </p>
<p>A quick analysis of the few available H3N2 hemagglutinin (a protein found on flu viruses) gene sequences from October to December 2017 reveal there was as much variability among this UK season’s H3N2 strains as seen between UK and Aussie strains. There are multiple strains.</p>
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<strong>
Read more:
<a href="https://theconversation.com/this-may-not-be-the-biggest-flu-season-on-record-but-it-is-a-big-one-here-are-some-possible-reasons-82642">This may not be the 'biggest flu season on record', but it is a big one – here are some possible reasons</a>
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<p>Studies show the <a href="https://theconversation.com/heres-why-the-2017-flu-season-was-so-bad-86605">flu vaccine</a>, which protects against three or four strains, performed unsatisfactorily against H3N2 in Australia last season. The vaccine strain was only 5-19% effective at protecting against circulating H3N2.</p>
<p>Vaccination remains our best defence against the multiple strains that surge during our flu season every year. Adding resources and pressure to <a href="http://www.nejm.org/doi/full/10.1056/NEJMp1714916#t=article">calls for improved vaccines</a> rather than where the vaccine target originated from are more likely to help to those who sicken and sometimes die from flu.</p>
<p><em>Update: since publication, the UK government released a <a href="https://www.gov.uk/government/statistics/weekly-national-flu-reports">new weekly national flu report</a>. This shows a continuing rise in detection of flu B cases. Flu B viruses now clearly dominate among confirmed flu cases in the UK, which differs from most of the Australian season.</em></p>
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<strong>
Read more:
<a href="https://theconversation.com/flu-vaccine-wont-definitely-stop-you-from-getting-the-flu-but-its-more-important-than-you-think-75778">Flu vaccine won't definitely stop you from getting the flu, but it's more important than you think</a>
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<img src="https://counter.theconversation.com/content/89960/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian M. Mackay has previoulsy received grant funding from NHMRC and ARC. </span></em></p><p class="fine-print"><em><span>Katherine Arden 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>There are many flu strains, and those strains can also change and mutate.Ian M. Mackay, Adjunct assistant professor, The University of QueenslandKatherine Arden, Virologist, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/796152017-06-27T12:17:05Z2017-06-27T12:17:05ZHow flu changes within the human body may hint at future global trends<figure><img src="https://images.theconversation.com/files/174656/original/file-20170620-24880-xnvg6g.png?ixlib=rb-1.1.0&rect=25%2C8%2C1822%2C1028&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">What can a single person's flu infection tell you about how the virus changes around the world?</span> <span class="attribution"><span class="source">Xue and Bloom</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Evolution is usually very slow, a process of change that takes thousands or millions of years to see.</p>
<p>But for influenza, evolution is fast – and deadly. Flu viruses <a href="https://www.cdc.gov/flu/about/viruses/change.htm">change rapidly</a> to escape the body’s defenses. Every few years, new variants of flu emerge and cause epidemics around the world.</p>
<p>Controlling the spread of flu means dealing with this ongoing evolution. Each year, <a href="http://www.who.int/influenza/en/">experts from the World Health Organization</a> (WHO) must make their best guess about how the virus will change in order to <a href="http://www.who.int/influenza/vaccines/virus/recommendations/en/">choose which flu strains</a> to include in the annual vaccine.</p>
<p>This work is difficult and uncertain, and mistakes have real consequences. Worldwide, <a href="http://www.who.int/mediacentre/factsheets/fs211/en/">flu infects several million people each year</a> and causes hundreds of thousands of deaths. In years when predictions miss the mark and the flu shot is very different from circulating strains, <a href="https://www.cdc.gov/flu/professionals/vaccination/effectivenessqa.htm">more people are vulnerable</a> to infection.</p>
<p>In the past several years, advances in genome sequencing have begun to shed light on the beginnings of viral evolution, deep within individual infections. We wondered whether, for flu, this information might give us an early glimpse of future global evolutionary trends.</p>
<p>What could a single person’s flu infection tell us about how the virus changes across the world? As it turns out, a surprising amount.</p>
<h2>Looking deep inside an infection</h2>
<p>Every step in flu’s evolution begins with a mistake. As viruses copy themselves within an infected person, they sometimes mutate, creating small changes to their genetic blueprint.</p>
<p><a href="https://doi.org/10.7554/eLife.03300">Most mutations are harmful to the virus</a> because they break the machinery it needs to function. But every so often, a mutant virus survives, and even thrives. Viruses play a constant game of cat-and-mouse with the human immune system. Sometimes, a mutant virus may be just different enough to escape the body’s notice.</p>
<p>A mutant virus with this kind of advantage can multiply quickly and come to dominate the infection. Eventually, it may even spread from person to person, and from there, start spreading around the world.</p>
<p>Recently, it’s become easier to track how viruses change within the human body. The same advances that have made it <a href="https://www.genome.gov/sequencingcosts/">cheap and easy</a> to sequence human genomes are changing how we study viruses. For the cost of sequencing a single human genome, we can sequence thousands of viruses from throughout an infection to track new mutations as they arise. </p>
<p>These mutations can show us how the virus reacts to challenging environments within the human body. For HIV, where infections often last years or even decades, <a href="https://doi.org/10.7554/eLife.11282">evolution can be substantial</a>, even within a single person. In particular, viruses often <a href="https://doi.org/10.7554/eLife.10670">evolve drug resistance</a> in response to antiviral treatment.</p>
<h2>Tracking flu evolution in four long infections</h2>
<p>We recently <a href="https://doi.org/10.7554/eLife.26875">tracked viral evolution in four cancer patients</a> who had flu infections lasting several months. Most flu infections last about a week, which limits the amount of change that can occur. But in patients with weak immune systems, infections can last a long time, with <a href="https://doi.org/10.1086/425004">severe effects</a>.</p>
<p>How did flu change within these long infections? By sequencing viruses from different times during the infection and comparing their genomes, we were able to identify new mutations and track their fates.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=389&fit=crop&dpr=1 600w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=389&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=389&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=489&fit=crop&dpr=1 754w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=489&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/175744/original/file-20170626-29070-1ec2px1.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=489&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">Each subplot represents one site in the virus where mutations can occur. Mutant viruses are shown in orange, and their frequencies rise and fall over time.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.7554/eLife.26875">Xue et al. eLife 2017;6:e26875</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Evolution acted in a matter of weeks. One clear example was resistance to Tamiflu. The patients we studied were taking the drug to control their infections. But, <a href="https://doi.org/10.1128/mBio.02464-14">as in prior studies</a>, viruses carrying drug-resistance mutations eventually emerged. These mutations might partly explain why the infections lasted so long.</p>
<p>Drug-resistance mutations weren’t the only evolutionary changes we saw. Half a dozen mutant viruses, all just slightly different from one another, would sometimes compete simultaneously in a single person.</p>
<p>These competing viruses made evolution a complicated affair. A mutation that started spreading one week would sometimes go extinct the next. Presumably, it was outcompeted by an even better mutation.</p>
<p>In some cases, we found the exact same mutations in viruses from different patients in our study, even though we could tell that the patients did not infect each other. We’d only very rarely expect such similarities to happen due to chance. The viruses may have hit on similar adaptations in response to evolutionary challenges. Some of these mutations may have helped the virus avoid the immune system, <a href="https://doi.org/10.1128/JVI.03248-15">echoing other studies</a>.</p>
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<figcaption><span class="caption">Author Katherine Xue explains her Ph.D. research on how flu evolves inside you.</span></figcaption>
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<h2>Forecasting the future</h2>
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<a href="https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/175732/original/file-20170626-29085-w7je28.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"></a>
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<span class="caption">The 3-D structure of influenza virus as imaged by electron tomography. The spike proteins poke out from the virus’ coat.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Steven_H3N2_Flu_ET.jpg">Audray Harris, Bernard Heymann and Alasdair C. Steven, LSBR, NIAMS, NIH</a></span>
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<p>What’s more, many mutations within these patients matched mutations that later spread around the world. In the spikes of flu’s outer coat, which help the virus enter host cells, the mutation N225D emerged in three of the four patients in our study. By 2015, about eight years after our patients were infected, most flu viruses around the world carried the exact same change.</p>
<p>For us, this was unexpected. Evolution is full of trade-offs, and some mutations that help flu adapt within people <a href="https://doi.org/10.1038/440435a">may slow its transmission</a> from person to person. We also didn’t know whether evolution in such unusually long flu infections would match patterns of change around the world. </p>
<p>But in our study, flu evolution in individual people showed striking similarities to evolution around the globe. We could see hints of some global evolutionary trends within just a few individuals.</p>
<p>As technologies continue to improve, it’s becoming easier to look deep inside flu infections, like we did. WHO labs <a href="http://www.who.int/influenza/gisrs_laboratory/en/">sequence flu strains</a> from thousands of people every year to monitor flu evolution. Researchers are sequencing more and more strains in ways that let us catch mutations as they first arise within individual people.</p>
<p>Each of these thousands of infections is like a separate evolutionary experiment. By comparing mutations that appear in different infections, we may get a sense of evolutionary possibilities and constraints.</p>
<p>Somewhere down the line, this kind of information may help forecast flu’s evolution. For now, at least, it’s uncovering some of the dynamic processes of evolution that take place within each of us.</p><img src="https://counter.theconversation.com/content/79615/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Katherine Xue is supported by the National Science Foundation and the Hertz Foundation. </span></em></p><p class="fine-print"><em><span>Jesse Bloom's research is supported by the NIH (NIAID and NIGMS), the Burroughs Wellcome Fund, and a Faculty Scholars grant from the HHMI and Simons Foundation.</span></em></p>New genetic technologies are letting us look at flu evolution right where it starts: within individual people, while they’re sick.Katherine Xue, Doctoral Student in Genome Sciences, University of WashingtonJesse Bloom, Associate Member, Fred Hutchinson Cancer Research Center and Affiliate Associate Professor of Genome Sciences and Microbiology, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/792582017-06-12T15:32:30Z2017-06-12T15:32:30ZDesigning antiviral proteins via computer could help halt the next pandemic<figure><img src="https://images.theconversation.com/files/173403/original/file-20170612-3809-17j4mj1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Computers may play an important role in preparing us for the next viral outbreak – whether flu or Ebola.</span> <span class="attribution"><span class="source">UW Institute for Protein Design</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>As Bill Gates sees it, there are three main threats to our species: nuclear war, climate change and the next global pandemic.</p>
<p>Speaking on pandemic preparedness at the Munich Security Conference earlier this year, <a href="http://www.businessinsider.com/bill-gates-op-ed-bio-terrorism-epidemic-world-threat-2017-2">Gates reminded us that</a> “the fact that a deadly global pandemic has not occurred in recent history shouldn’t be mistaken for evidence that a deadly pandemic will not occur in the future.”</p>
<p>If we want to be prepared for the worst, Gates says, “first and most importantly, we have to build an arsenal of new weapons – vaccines, drugs and diagnostics.”</p>
<p>Some scientists are now using computers to do just that.</p>
<h2>Going beyond the immune system</h2>
<p>Despite the availability of the flu shot, the World Health Organization <a href="http://www.who.int/mediacentre/factsheets/fs211/en/">reports that seasonal influenza</a> is still responsible for millions of serious illnesses and as many as half a million deaths per year globally. The <a href="https://www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm">partial efficacy</a> of each year’s flu shot, coupled with <a href="https://doi.org/10.1016/S0264-410X(03)00071-9">long manufacturing times</a> and <a href="https://doi.org/10.1016/j.vaccine.2015.08.082">limited global availability</a>, suggests new flu-fighting methods are still needed.</p>
<p>And that’s just for the seasonal flu. Pandemic influenza, like the devastating 1918 Spanish flu, could again kill tens of millions of people in a single year.</p>
<p>Antibodies, a natural part of the immune system, are front-line soldiers in the war against viruses. The job of an antibody is to recognize and physically adhere to a foreign invader like influenza. Human antibodies are bivalent, meaning they have two hands with which they can grab onto their target.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/173274/original/file-20170611-21746-vge57m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/173274/original/file-20170611-21746-vge57m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/173274/original/file-20170611-21746-vge57m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=608&fit=crop&dpr=1 600w, https://images.theconversation.com/files/173274/original/file-20170611-21746-vge57m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=608&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/173274/original/file-20170611-21746-vge57m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=608&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/173274/original/file-20170611-21746-vge57m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=764&fit=crop&dpr=1 754w, https://images.theconversation.com/files/173274/original/file-20170611-21746-vge57m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=764&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/173274/original/file-20170611-21746-vge57m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=764&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 glass model of an influenza virus hanging in the Smithsonian National Museum of Natural History.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/timevanson/7283938244">Tim Evanson</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Under a microscope, influenza looks like a tiny ball with spikes. It uses some of its surface spikes to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC553023/">break into human cells</a>. By grabbing tightly to those spikes using one or both hands, antibodies can <a href="https://doi.org/10.1126/science.1205669">prevent flu particles from infecting human cells</a>. But every year the rapidly evolving influenza picks up mutations in its spike proteins, causing the sticky hands of our antibodies to <a href="https://doi.org/10.1038/nrmicro1819">no longer recognize the virus</a>.</p>
<p>Researchers have long sought a <a href="https://doi.org/10.3390/v6103809">universal flu vaccine</a> – one that doesn’t need to be readministered every year. Efforts to produce one tend to involve injecting noninfectious flu lookalikes in hopes that it will prime the immune system to mount a proper attack on whatever real strain of flu it sees next. <a href="https://theconversation.com/influenza-the-search-for-a-universal-vaccine-68947">Despite some progress</a>, researchers have not yet been able to coax the immune system to defend against all strains of influenza, and the threat of a global pandemic still looms.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/173405/original/file-20170612-3809-19yqc5w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/173405/original/file-20170612-3809-19yqc5w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/173405/original/file-20170612-3809-19yqc5w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=390&fit=crop&dpr=1 600w, https://images.theconversation.com/files/173405/original/file-20170612-3809-19yqc5w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=390&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/173405/original/file-20170612-3809-19yqc5w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=390&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/173405/original/file-20170612-3809-19yqc5w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=491&fit=crop&dpr=1 754w, https://images.theconversation.com/files/173405/original/file-20170612-3809-19yqc5w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=491&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/173405/original/file-20170612-3809-19yqc5w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=491&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Transmission electron microscopic image of an influenza virus particle.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Influenza_virus_particle_color.jpg">CDC/ Erskine. L. Palmer, Ph.D.; M. L. Martin</a></span>
</figcaption>
</figure>
<h2>Software to beat the flu</h2>
<p>Computational protein design offers another way. Rather than relying on the immune system to generate an antibody protein capable of shutting down a virus like the flu, computer modeling can now help quickly create custom antiviral proteins programmed to shut down a deadly virus.</p>
<p>Unlike a vaccine, this class of drug could be administered to treat an existing infection or given days prior to exposure to prevent one. And because these designer proteins work independently of the immune system, their potency does not depend on having an intact immune system – a useful trait, as those with weaker immune systems <a href="http://www.who.int/mediacentre/factsheets/fs211/en/">are at high risk for viral infection</a>.</p>
<p>Computer-generated antiviral proteins work the same way some natural proteins in our immune system do. By having surfaces that are chemically complementary to their targets, antiviral proteins can stick tightly to a specific virus. If a protein sticks to a virus in just the right way, it can physically block how that virus moves, ultimately preventing infection.</p>
<p>By designing an antiviral protein on a computer, building it in the laboratory and then administering it into the body, you effectively digitize part of the immune system.</p>
<p>In 2016, computer-generated proteins were shown to be <a href="https://doi.org/10.1371/journal.ppat.1005409">more effective than oseltamivir (Tamiflu) in warding off death</a> in influenza-infected mice. One dose of designer protein given intranasally was more effective than 10 doses of Tamiflu, a drug considered an “essential medicine” by the WHO due to its antiflu activity. What’s more, these new computer-generated antiflu proteins protected mice against diverse strains of the flu. Efforts to turn these promising results into FDA-approved drugs <a href="https://virvio.com/">are underway</a>.</p>
<p>In a <a href="https://doi.org/10.1038/nbt.3907">just published paper</a> in Nature Biotechnology, scientists here at the <a href="http://www.ipd.uw.edu">Institute for Protein Design</a> at the University of Washington went a step further and demonstrated a new way to shut down the flu: They used computer modeling to build a completely new kind of antiviral protein with three sticky hands.</p>
<p>Why three? It turns out many deadly envelope viruses – like influenza, Ebola and HIV – build their spike proteins out of three symmetric parts.</p>
<p>A single antiviral drug with three properly spaced hands should be able to symmetrically grab each part of a spike protein, leading to tighter binding and overall better antiviral activity. This geometric feat is beyond what the human immune system can naturally do.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/173302/original/file-20170611-4841-o60aj2.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/173302/original/file-20170611-4841-o60aj2.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/173302/original/file-20170611-4841-o60aj2.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=240&fit=crop&dpr=1 600w, https://images.theconversation.com/files/173302/original/file-20170611-4841-o60aj2.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=240&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/173302/original/file-20170611-4841-o60aj2.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=240&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/173302/original/file-20170611-4841-o60aj2.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=302&fit=crop&dpr=1 754w, https://images.theconversation.com/files/173302/original/file-20170611-4841-o60aj2.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=302&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/173302/original/file-20170611-4841-o60aj2.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=302&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Left: The tips of many viral spike proteins are built out of three symmetric parts, with one part highlighted in pink. Right: A new three-handed antiflu protein (blue) bound to influenza’s HA spike.</span>
<span class="attribution"><span class="source">UW Institute for Protein Design</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>The design strategy worked. The best three-handed protein, called Tri-HSB.1C, was able to bind tightly to diverse strains of influenza. When given to mice, it also afforded complete protection against a lethal flu infection with only minimal associated weight loss – a trait commonly used to diagnose flu severity in mice. Researchers are now applying the same tools to the Ebola spike protein.</p>
<p>It will be many years before this new technology is approved for use in humans, for any virus. But we may not have to wait long to see some lifesaving benefits.</p>
<h2>Viral diagnostics</h2>
<p>By coating a strip of paper with a three-handed flu binder and applying influenza samples on top, the same team was able to detect the presence of viral surface protein even at very low concentrations. This proof-of-concept detection system <a href="https://doi.org/10.1021/acs.analchem.7b00769">could be transformed</a> into a reliable and affordable on-site diagnostic tool for a variety of viruses by detecting them in saliva or blood. Like a pregnancy test, a band on a test strip could indicate flu. Or Ebola. Or the next rapidly spreading global pandemic.</p>
<p>In a 2015 letter to the New England Journal of Medicine on lessons learned from the Ebola epidemic in West Africa, Bill Gates describes the lack of preparation by the global community as “<a href="https://doi.org/10.1056/NEJMp1502918">a global failure</a>.”</p>
<p>“Perhaps the only good news from the tragic Ebola epidemic,” Gates says, “is that it may serve as a wake-up call.” (The Bill and Melinda Gates Foundation funds work on protein design at the University of Washington.)</p>
<p>When a global viral pandemic like the 1918 Spanish flu strikes again, antivirus software of the biological kind may play an important role in saving millions of lives.</p><img src="https://counter.theconversation.com/content/79258/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Haydon is a doctoral student at the University of Washington's Institute for Protein Design, which receives funding from the Bill and Melinda Gates foundation.</span></em></p>This antivirus software protects health, not computers. Researchers are beginning to combat deadly infections using computer-generated antiviral proteins – a valuable tool to fight a future pandemic.Ian Haydon, Doctoral Student in Biochemistry, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/689472017-01-12T02:12:30Z2017-01-12T02:12:30ZInfluenza: The search for a universal vaccine<p>No one wants to catch the flu, and the best line of defense is the seasonal influenza vaccine. But producing an effective annual flu shot relies on accurately predicting which flu strains are most likely to infect the population in any given season. It requires the coordination of multiple health centers around the globe as the virus travels from region to region. Once epidemiologists settle on target flu strains, vaccine production shifts into high gear; it takes <a href="https://www.cdc.gov/flu/about/season/vaccine-selection.htm">approximately six months</a> to generate the <a href="https://www.cdc.gov/flu/professionals/vaccination/vaccinesupply.htm">more than 150 million injectible doses</a> necessary for the American population.</p>
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<p>Incorrect or incomplete epidemiological forecasting can have major consequences. In 2009, while <a href="http://www.who.int/influenza/Influenza_vaccine_manufacturers2009_05.pdf">manufacturers, including MedImmune and Sanofi Pasteur</a>, were preparing vaccines against the anticipated strains, an <a href="https://www.cdc.gov/h1n1flu/cdcresponse.htm#A_Pandemic_Is_Declared">additional influenza strain, H1N1</a>, emerged. The prepared vaccine didn’t protect against this unanticipated strain, causing worldwide panic and over 18,000 confirmed deaths – likely only a fraction of the true number, <a href="http://dx.doi.org/10.1016/S1473-3099(12)70121-4">estimated to exceed 150,000</a>. Better late than never, a vaccine was eventually produced against H1N1, requiring a second flu shot that year.</p>
<p>Given that influenza has caused the majority of <a href="https://www.cdc.gov/flu/pandemic-resources/basics/past-pandemics.html">pandemics over the past 100 years</a> – including the 1918 flu that <a href="http://doi.org/10.1353/bhm.2002.0022">resulted in as many as 50 million deaths</a> – we’re left with the question: Can scientists produce a “universal” vaccine capable of protecting against diverse strains of influenza, one that doesn’t require annual predictions by epidemiologists and a yearly shot for you? </p>
<h2>Vaccines prime the immune system to fight</h2>
<p>By the 18th century, and arguably much earlier in history, it was commonly known that a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/">survivor of smallpox would not come down with it again</a> upon subsequent exposure. Somehow, infection conferred immunity against the disease. And people recognized that milkmaids who came into contact with cowpox-ridden cattle would similarly be protected from smallpox.</p>
<p>In the late 1700s, farmer <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/">Benjamin Jesty inoculated his family with cowpox</a>, effectively immunizing them against smallpox, despite future exposure. Physician <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC495097/">Edward Jenner then catapulted humanity into a new age of immunology</a> when he lent scientific credence to the procedure.</p>
<p>So if one inoculation of cowpox or one exposure to (and survival of) smallpox confers a decade’s-worth or even lifelong immunity, why are individuals encouraged to receive the flu vaccine every year? </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=471&fit=crop&dpr=1 600w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=471&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=471&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=592&fit=crop&dpr=1 754w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=592&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/152325/original/image-20170110-29000-ditp3r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=592&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An artist’s rendition of the anatomy of a virus.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/wellcomeimages/30738089686">Anna Tanczos/Wellcome Images</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>The answer lies in how quickly the influenza virus’ anatomy changes. Each virus consists of a roughly spherical membrane encapsulating constantly mutating genetic material. This membrane is peppered with two types of “spikes”: hemagglutinin, or HA, and neuraminidase, or NA, each made up of a stem and a head. HA and NA help the virus with infection by binding to host cells, and mediate the entry of the virus into the cell and eventually its exit.</p>
<p>Vaccines typically elicit antibodies that target these two molecules. Once injected, an individual’s immune system gets to work. Specialized cells collect the vaccine molecules as invaders; other cells then generate antibodies that will recognize the foreign molecules. The next time those same invaders show up – whether in the form of the same vaccine or the virus strains it mimicked – the body’s immune cells recognize them and fight them off, preventing infection.</p>
<p>For vaccine developers, one frustrating characteristic about influenza’s mutating genome is how rapidly HA and NA change. These constant alterations are what send them back to the drawing board for novel vaccines every flu season.</p>
<h2>Different methods to design a vaccine</h2>
<p>The smallpox vaccine was the first to use the “empirical paradigm” of vaccinology – the same strategy we largely use today. It relies on a trial-and-error approach to mimic the immunity induced by natural infection.</p>
<p>In other words, vaccine developers believe the body will mount an antibody response to something in the inoculation. But they don’t focus on which specific patch of the virus is causing an immune response. It doesn’t really matter if it’s a reaction to a small patch of HA that many strains share, for instance. When using an entire virus as starting material, it’s possible to get many different antibodies recognizing many different parts of the virus used in the vaccine.</p>
<p>The seasonal flu shot generally fits into this empirical approach. Each year, epidemiologists forecast which flu strains are most likely to infect populations, typically settling on three or four. Researchers then attenuate or inactivate these strains so they can act as the mimics in that year’s influenza vaccine without giving recipients the full-blown flu. The hope is that an individual’s immune system will respond to the vaccine by creating antibodies that target these strains; then when he or she comes into contact with the flu, the antibodies will be waiting to neutralize those strains. </p>
<p>But there’s a different way to design a vaccine. It’s called rational design and represents a potentially game-changing paradigm shift in vaccinology. </p>
<p>The goal is to design some molecule – or “immunogen” – that can cause effective antibodies to be produced without requiring exposure to the virus. Relative to current vaccines, the engineered immunogen may even allow for more specific responses, meaning the immune response targets particular parts of the virus, and greater breadth, meaning it could target multiple strains or even related viruses.</p>
<p>This strategy works to target specific epitopes, or patches of the virus. Since antibodies work by recognizing structures, the designers want to emphasize to the immune system the structural properties of the immunogens they’ve created. Then researchers can try to design candidate vaccines with those structures in hopes they’ll provoke the immune system to produce relevant antibodies. This path might let them assemble a vaccine that elicits a more effective and efficient immune response than would be possible with the traditional trial-and-error method.</p>
<p>Promising headway has been made in <a href="http://doi.org/10.1038/nature12966">vaccine design for respiratory syncytial virus</a> using this new rational paradigm, but efforts are still underway to use this approach for influenza.</p>
<h2>Toward a universal flu vaccine</h2>
<p>In recent years, researchers have isolated a number of potent, infleunza-neutralizing antibodies produced in our bodies. While the antibody response to influenza is <a href="http://doi.org/10.1128/JVI.03562-13">primarily directed at the head of the HA spike</a>, several have been found that <a href="http://doi.org/10.1038/nsmb.1566">target HA’s stem</a>. Since the stem is more constant across viral strains than the head, this could be flu’s Achilles’ heel, and antibodies that target this region may be a good template for vaccine design.</p>
<p>Researchers are pursuing a number of approaches that could cause the body to produce these antibodies of interest before becoming infected. One strategy, known as nanoparticle display, involves designing a molecule that incorporates part of the virus. In the lab, scientists could attach some combination of HA and NA particles to the outside of a spherical nanoparticle that itself is capable of causing an immune response. When injected as part of a vaccine, the immune system could “see” these molecules, and with luck produce antibodies against them. </p>
<p>One of the major questions that needs to be answered is what exactly should be displayed on the exterior of these nanoparticles. Some strategies display various versions of full HA molecules, while others just include stems. While more data on humans need to be collected to validate these approaches, the data from animal studies using <a href="http://doi.org/10.1038/nm.3927">stem-only immunogens are encouraging</a>.</p>
<p>With current technology, there may never be a “one and done” flu shot. And epidemiological surveillance will always be necessary. However, it is not inconceivable that we can move from a once-per-year model to a once-every-10-years approach, and we may be within just a few years of being there.</p><img src="https://counter.theconversation.com/content/68947/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Setliff receives funding support from the NIH and volunteers for the TJ Martell Foundation, the American Cancer Society, and Nashville's Joint Community Advisory Board for the HIV Vaccine Trials Network and AIDS Clinical Trials Group.</span></em></p><p class="fine-print"><em><span>Amyn Murji receives funding from the NIH. </span></em></p>Flu virus mutates so quickly that one year’s vaccine won’t work on the next year’s common strains. But a new way to create vaccines, called ‘rational design,’ might pave the way for more lasting solutions.Ian Setliff, Ph.D. Student, Program in Chemical & Physical Biology, Vanderbilt Vaccine Center, Vanderbilt UniversityAmyn Murji, Ph.D. Student, Department of Microbiology and Immunology, Vanderbilt Vaccine Center, Vanderbilt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/606742016-07-27T21:20:13Z2016-07-27T21:20:13ZGMOs lead the fight against Zika, Ebola and the next unknown pandemic<figure><img src="https://images.theconversation.com/files/132228/original/image-20160727-21595-158l7x3.jpg?ixlib=rb-1.1.0&rect=0%2C646%2C5748%2C4122&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">GMOs may very well have filled up that syringe.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-336640973/stock-photo-hand-with-a-syringe-injection-vaccination-medicine-pop-art-retro-style.html?src=pp-same_artist-346093292-5N0wHCvzYAJ7L24IKgcP_g-2&ws=1">Syringe image via www.shutterstock.com</a></span></figcaption></figure><p>The shadow of the Zika virus hangs over the Rio Olympic Games, with visitors and even <a href="http://www.telegraph.co.uk/sport/0/rio-olympics-which-athletes-have-withdrawn-over-zika-fears/">high-profile athletes citing worries</a> about Zika as a reason to stay away (even if the <a href="https://theconversation.com/the-olympics-wont-spread-zika-around-the-world-62822">risk is probably quite low</a>). The public’s concerns are a striking example of the need to rapidly combat emerging infectious diseases.</p>
<p>In the fight against <a href="https://www.cdc.gov/zika/">Zika</a>, public health experts have turned to what may sound like an unlikely ally: genetically modified organisms, or <a href="http://gmo.geneticliteracyproject.org/FAQ/what-are-gmos/">GMOs</a>.</p>
<p>Consumers are used to hearing about GMOs in food crops, but may be unaware of the vital role GMOs play in medicine. Most modern biomedical advances, especially the vaccines used to eradicate disease and protect against pandemics such as Zika, <a href="https://www.cdc.gov/vhf/ebola/">Ebola</a> and the <a href="http://www.flu.gov">flu</a>, rely on the same molecular biology tools that are used to create genetically modified organisms. To protect the public, scientists have embraced GMO technology to quickly study new health threats, manufacture enough protective vaccines, and monitor and even predict new outbreaks. </p>
<h2>Vaccines, meet molecular biology</h2>
<p>Vaccines work with the immune system to strengthen the body’s own natural defenses. A vaccine offers a preview of a potential infection, so the immune system is ready to pounce if the real threat shows up. </p>
<p>The earliest vaccines were primitive – think Edward Jenner in the 1790s <a href="http://www.jennermuseum.com/vaccination.html">inoculating against smallpox</a> by rubbing together the open wounds of uninfected patients and those with cowpox. But over the years, advances in medical technology led to improved vaccines. The modern age of vaccines was ushered in by the introduction of <a href="http://www.jove.com/science-education-database/2/basic-methods-in-cellular-and-molecular-biology">molecular biology tools</a> in the 1970s, which vastly improved our ability to study and manipulate viruses.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=513&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=513&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=513&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=644&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=644&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=644&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Viruses have spikes for attaching to host cells and a cargo bay to hold its genes (red).</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic.mhtml?id=387259318">Virus illustration via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<p>Under the microscope, viruses look like spiky balls, with an internal cargo bay that houses their genetic material. “Dissecting” a virus means using molecular biology tools to study its genes (whether encoded via DNA or RNA) up close. For example, researchers can “cut and paste” genes to study them in isolation and figure out what they do. Or researchers can cause genetic mutations and watch how an organism responds.</p>
<p>When DNA is modified or studied inside different cells than those from which it originated, it is called “<a href="https://www.britannica.com/science/recombinant-DNA-technology">recombinant DNA</a>.” An organism with recombinant DNA is considered a GMO.</p>
<p>GMO developers use molecular biology, manipulating genes to study and alter plant DNA, for instance, to create new varieties that can thrive with <a href="https://www.geneticliteracyproject.org/wp-content/uploads/2013/07/Biotechnology-infographic_7.29.13-clean.pdf">less water or fewer pesticides</a>.</p>
<p>For vaccine researchers, molecular biology is a jack-of-all-trades. These tools allow scientists to figure out the keys to a virus’ survival by dissecting its DNA, devise new vaccines, manufacture those vaccines cheaply and quickly, and monitor which viruses in the wild might become public health headaches. According to <a href="http://medschool.umaryland.edu/FACULTYRESEARCHPROFILE/viewprofile.aspx?id=25096">Dr. José Esparza</a>, president of the <a href="http://gvn.org/">Global Virus Network</a> and professor at University of Maryland Medical School, “It is impossible to do research in biomedicine without doing molecular biology.”</p>
<h2>GMOs advance science of vaccines</h2>
<p>One disease currently being addressed with the help of molecular biology is <a href="http://www.who.int/mediacentre/factsheets/fs204/en/">hepatitis B</a>, which kills one person every minute worldwide – even though we do have an effective vaccine.</p>
<p>In the 1960s, virologists realized that the hepatitis B antigen – a protein from the virus’ outer shell that triggers an immune response in an infected person – showed up in the blood of hepatitis B patients. To their surprise, injecting a healthy person with the purified antigen protected against future infections. The first hepatitis B vaccine (<a href="http://www.nasonline.org/publications/beyond-discovery/hepatitis-b-story.pdf">HBV</a>), approved in 1981, was made by harvesting the antigen from the blood of hepatitis B carriers, including intravenous drug users.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.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">Administering the hepatitis B vaccine to a child at a rural health center in India.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/unitednationsdevelopmentprogramme/4968223306">United Nations Development Programme</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
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</figure>
<p>Once recombinant DNA technology was developed, researchers could isolate the gene for the virus’ antigen protein, allowing for HBV to be manufactured in laboratories via those genetic instructions instead of from infected blood. Currently, both FDA-approved <a href="https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/appdx-full-b.pdf">vaccines for hepatitis B</a> include the recombinant version of the antigen. </p>
<p>And molecular biology can be used to accelerate the development of new vaccines. For example, in late June, a “<a href="https://www.statnews.com/2016/06/20/zika-vaccine-inovio/">DNA vaccine</a>” was the first to be approved for human trials against the Zika virus. Rather than containing the Zika antigen itself, the vaccine contains a gene for the Zika antigen which the patient’s body then produces.</p>
<p>The announcement of this breakthrough came less than five months after the World Health Organization declared Zika a “<a href="http://www.who.int/mediacentre/news/statements/2016/emergency-committee-zika-microcephaly/en/">public health emergency of international concern</a>.” Without the tools to modify and isolate sections of DNA, Dr. Esparza of the Global Virus Network notes, “we would not be able to do this with the necessary speed and efficiency.”</p>
<h2>GMOs as pharma factories</h2>
<p>Consumers who scrupulously avoid genetically modified foods might be surprised to know that lots of <a href="https://gmoanswers.com/studies/gmos-food-and-medicine-overview">drugs and vaccines</a> they rely on are the product of GMOs.</p>
<p>Many vaccines and top-grossing pharmaceuticals contain proteins as the main ingredient. Proteins are <a href="http://dx.doi.org/10.3389/fmicb.2014.00172">too costly</a> and delicate to manufacture from scratch. But living cells must make proteins to survive, and they can be coaxed to produce medical proteins in bulk, requiring little more than the DNA instructions and sugary broth as fuel. Since these genetic blueprints must be inserted into the cells, many vaccines and drugs are technically the product of GMOs. </p>
<p>Modified bacteria, yeast and even <a href="https://biotechhistory.org/magazine-article/vital-tools-brief-history-cho-cells/">Chinese hamster cells</a> are the unheralded molecular factories of the drug and vaccine industry. In 2014, 10 of the <a href="http://cellculturedish.com/2015/03/10-biologics-on-best-selling-drugs-list-for-2014/">top 25 best-selling drugs</a> were “<a href="http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm133077.htm">biologics</a>” – drugs made up of recombinantly produced proteins – including blockbuster treatments for arthritis, cancer and diabetes. Of the 10 vaccines that the <a href="https://www.cdc.gov/vaccines/parents/downloads/parent-ver-sch-0-6yrs.pdf">Centers for Disease Control and Prevention (CDC) recommends</a> for newborns, three are available in recombinant form; HBV, for example, is produced by modified yeast. The earliest recombinant vaccines and drugs have been in use for <a href="http://www.biotechnology.amgen.com/timeline.html">three decades</a>. </p>
<p>Perhaps the most dramatic example of GMO use in medicine came during the 2014 Ebola outbreak in West Africa. When American doctor Kent Brantly and other Western volunteers contracted Ebola, several were cured by a “<a href="http://wgntv.com/2014/08/04/secret-serum-likely-saved-ebola-patients/">secret serum</a>” called <a href="http://doi.org/10.1038/nature13777">Zmapp</a>. Manufactured by <a href="http://www.fastcompany.com/3045741/most-creative-people-2015/meet-ebolas-soft-spoken-plant-loving-arch-nemesis">genetically modified tobacco plants</a>, it’s a mixture of several proteins that attack the Ebola virus.</p>
<p>The technology for producing drugs in genetically modified plants, dubbed “pharming,” was developed by <a href="https://sols.asu.edu/people/charles-arntzen">Charles Arntzen</a> in the early 1990s. In the case of Zmapp, the antibodies are made in the tobacco plant’s leaves. When they’re harvested, rather than being made into cigarettes, their cells are popped open and the drug is collected. Researchers call pharming “<a href="http://www.fastcompany.com/3045741/most-creative-people-2015/meet-ebolas-soft-spoken-plant-loving-arch-nemesis">a revolution for the field</a>” of manufacturing pharmaceuticals.</p>
<p>The biotech company <a href="http://www.appliedbiotech.org">Applied Biotechnology Institute</a> has embraced the technique to make a next-generation pharmed vaccine. They’re developing a genetically modified corn plant that produces the hepatitis B antigen. The plant could be harvested and turned into an oral vaccine tablet, which looks like a small wafer, as opposed to a liquid which must be refrigerated and injected. The hope is that an oral vaccine can lower the rates of hepatitis B in the developing world, where the cold supply chain, sanitary needles and trained medical personnel the current vaccine depends on are either lacking or prohibitively expensive.</p>
<h2>Future of diagnostics</h2>
<p>Beyond improved vaccines, equally pressing for the future of public health will be addressing pandemics that have not yet even begun. Virologist Esparza counts 11 pandemics that have occurred in the last 14 years, including Ebola, the <a href="http://www.flu.gov/about_the_flu/h1n1/">H1N1 (swine) flu</a> and <a href="https://www.cdc.gov/coronavirus/mers/">MERS</a> – all but one of which were viruses. “It is totally predictable there will be other pandemics. What is not easy to predict is which one. Two years ago, no one could have predicted Zika,” he told me.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Molecular biology technology has made possible simple diagnostic tools, like this paper-based test for Zika. Areas that have turned purple indicate samples infected with the virus.</span>
<span class="attribution"><span class="source">Wyss Institute at Harvard University</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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</figure>
<p>Molecular biology is often found on the front lines of pandemics, appearing in on-the-spot diagnostic tools that are cheap and do not require extensive equipment or training. For example, a Harvard-led team <a href="http://dx.doi.org/10.1016/j.cell.2016.04.059">recently unveiled</a> a <a href="http://www.forbes.com/sites/jenniferhicks/2016/05/09/researchers-develop-low-cost-paper-diagnostic-test-for-zika-virus/#24ee99f53fb4">paper-based test</a> – similar to a pregnancy test – that uses the <a href="https://theconversation.com/crispr-cas-gene-editing-technique-holds-great-promise-but-research-moratorium-makes-sense-pending-further-study-43371">CRISPR/Cas</a> gene editing tool to distinguish the Zika virus from the closely related <a href="https://www.statnews.com/2016/02/17/zika-dengue-infections/">Dengue virus</a>. If the Cas9 protein encounters the specific DNA sequence of Zika virus in a drop of blood, it starts a chain reaction that results in a colored readout.</p>
<p>Beyond diagnosing single patients, molecular biology tools will be used to get ahead of the as-yet-unknown pandemic threats that lie in the future. Public health officials are <a href="http://www.who.int/csr/alertresponse/en/">calling for monitoring infections</a> in the places where new diseases frequently emerge. Quick and accurate diagnostic tests are key to determining which viruses are already circulating and would allow researchers to anticipate new pandemics and develop and stockpile vaccines. </p>
<p>“Until now, we have had a very reactive response” to threats like Zika and Ebola, says Dr. Esparza. With the help of GMOs, infectious disease experts have the tools to get ahead of the next outbreak, moving beyond reaction to quick detection, containment and even prevention.</p><img src="https://counter.theconversation.com/content/60674/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeff Bessen works in a molecular biology lab that has received funding on various projects from the NIH, HHMI, and DARPA. The lab has received funding from Monsanto for a project unrelated to vaccines and medicines.
</span></em></p>Public health experts enlist the molecular biology tools that create genetically modified organisms – as well as the GMOs themselves – in the fight against emerging infectious diseases.Jeff Bessen, Ph.D. Candidate in Chemical Biology, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/506922015-11-16T11:59:49Z2015-11-16T11:59:49ZWhy have people turned their backs on the flu vaccine this year?<figure><img src="https://images.theconversation.com/files/101940/original/image-20151115-10412-3iv5e1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Why the low uptake?</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&autocomplete_id=&searchterm=injection%20in%20arm&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=317932724">www.shutterstock.com</a></span></figcaption></figure><p>Slow uptake of the seasonal flu vaccine could leave thousands of people at increased risk of infection. According to the Royal College of General Practitioners, the number of flu vaccinations delivered so far this year is down 6% on last year. And uptake is low across a <a href="https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/476569/PHE_Influenza_Surveillance_graphs_15_16_wk46.pdf">range of vulnerable groups</a> including the over-65s, children under five, and those with serious long-term health conditions such as chronic heart, lung or kidney disease.</p>
<p>We don’t know why the uptake has been so low, but we do know the reasons why this has been the case in previous years. They include <a href="http://www.sciencedirect.com/science/article/pii/S0264410X11010012">concerns about the safety</a> of the vaccine and false beliefs that the side-effects of the vaccine are worse than the actual disease. Some may also not believe that they are at risk from the disease <a href="http://bjgp.org/content/61/588/e386.abstract">or are sceptical</a> about the value of vaccination. Another factor, related to the low effectiveness of the vaccine during last year’s flu season, may have contributed.</p>
<h2>How flu vaccines are developed</h2>
<p>Each year, a global flu surveillance team - with input from WHO (World Health Organisation) flu labs in Atlanta, London, Melbourne and Tokyo - tries to predict which strains of the virus are most likely to be prevalent in the coming year. Information from the analysis of thousands of influenza viruses identified by the different laboratories is pooled and, on the basis of this, the <a href="http://www.who.int/influenza/vaccines/en/">WHO</a> advises governments on the vaccine composition for the next season. </p>
<p>Three key strains of flu virus are identified by WHO to be incorporated into a “trivalent” vaccine that <a href="https://theconversation.com/a-universal-flu-vaccine-is-still-some-time-off-18525">will tackle the predicted forthcoming strains</a>. These recommendations are made six months in advance of the flu season so that pharmaceuticals companies have enough time to make and distribute the vaccine.</p>
<h2>One bad year</h2>
<p>During the 2014-15 flu season, the effectiveness of the vaccine in the UK was found to be poor – <a href="https://www.gov.uk/government/news/flu-vaccine-shows-low-effectiveness-against-the-main-circulating-strain-seen-so-far-this-season">a mere 3%</a>. This compares unfavourably with previous years where effectiveness rates were usually around 50%. It is possible that the low rates of effectiveness reported could have diminished both the public and health professionals’ confidence in the vaccine. </p>
<p>The effectiveness of the flu vaccine depends on a number of things, including the coverage of vaccination and the efficacy of the vaccine. Although the vaccine can provide moderate protection against the flu, the level of protection can vary widely from season to season. On average, flu vaccine efficacy is estimated to be around <a href="http://www.sciencedirect.com/science/article/pii/S147330991170295X">59% in adults and 83% in children</a>. Higher levels of effectiveness are achieved in years when there is a good match between the vaccine and the circulating strains of flu virus. </p>
<h2>Science and luck</h2>
<p>The predictions about which flu strains are likely to be the most prevalent depend as much on luck as it does science. Sometimes, as in the 2014-15 flu season in the UK, the predictions can go horribly wrong. In this case, the vaccine offered poor protection against flu infection caused by one particular subtype of virus: <a href="https://www.gov.uk/government/news/flu-vaccine-shows-low-effectiveness-against-the-main-circulating-strain-seen-so-far-this-season">A(H3N2)</a>. </p>
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<img alt="" src="https://images.theconversation.com/files/101942/original/image-20151115-10401-1iiwrp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/101942/original/image-20151115-10401-1iiwrp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/101942/original/image-20151115-10401-1iiwrp8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/101942/original/image-20151115-10401-1iiwrp8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/101942/original/image-20151115-10401-1iiwrp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/101942/original/image-20151115-10401-1iiwrp8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/101942/original/image-20151115-10401-1iiwrp8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&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">I hope I predicted the right flu strains this year.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&autocomplete_id=&searchterm=luck&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=183924554">www.shutterstock.com</a></span>
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<p>The main reason for this is that the genetic make-up of the flu virus is unstable and new strains and variants are constantly emerging. If the emerging strain is different enough from the ones predicted to be a problem by WHO, this can make the vaccine ineffective. By the time it is apparent that the vaccine is ineffective - usually around mid-flu season - it is too late to develop a new vaccine to tackle the new strain of flu. </p>
<h2>Not a trivial illness</h2>
<p>One commonly held belief is that flu is not a serious condition. A lot of people <a href="https://theconversation.com/five-common-misconceptions-about-seasonal-flu-35683">mistake the common cold as flu</a>. But the flu is highly contagious, and infection can lead on to severe illnesses including pneumonia. In groups of people at high risk of being infected with the virus (due to poor immune systems), such as the elderly and those with existing health problems, the flu <a href="http://www.nhs.uk/Conditions/Flu/Pages/Complications.aspx">can cause considerable harm</a> and even death – especially in the elderly.</p>
<p>The flu vaccine can protect people from getting the flu, or it can make the disease milder in those who become infected. Those are the direct benefits of the vaccine. But there is also indirect protection. </p>
<h2>Herd immunity</h2>
<p>Between 56% and 73% of the population <a href="http://www.sciencedirect.com.eresources.shef.ac.uk/science/article/pii/S0264410X12003829">is protected indirectly</a> by flu vaccines, through what’s known as “herd immunity”. Herd immunity helps to break the disease’s chain of transmission because too few people are susceptible for the disease to be passed on. Lower vaccination uptake lowers this indirect protection. </p>
<p>One estimate was that as many as 1.2m cases of flu may be prevented each year in the UK by flu vaccination. Flu vaccination has been reported to reduce deaths <a href="http://www.sciencedirect.com/science/article/pii/S0264410X12003829">in the over-65s by 4.6%</a> and <a href="http://www.sciencedirect.com/science/article/pii/S0264410X10012703">reduces hospital admissions</a> for pneumonia and flu by around 8.5%. </p>
<p>In recent years there has been a good match between the vaccine and the circulating strains of flu. The 2014-15 flu season was an unfortunate blip. Hopefully, people won’t be put off by this one wrong prediction because the consequences of poor vaccine uptake could be huge.</p><img src="https://counter.theconversation.com/content/50692/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Lee also works for Public Health England as a Consultant in Communicable Disease Control.</span></em></p>If people are avoiding the flu jab because last year’s protection wasn’t great, that would be a mistake.Andrew Lee, Senior Clinical University Teacher & Consultant in Communicable Disease Control, University of SheffieldLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/427512015-09-08T03:38:37Z2015-09-08T03:38:37ZWhen should you take antibiotics?<figure><img src="https://images.theconversation.com/files/93865/original/image-20150904-7056-19ggbci.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The more we take antibiotics, the more likely we are to have superbugs down the line.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/timshelyn/5700493494/">Brandice Schnabel/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p><a href="https://theconversation.com/we-need-new-antibiotics-to-beat-superbugs-but-why-are-they-so-hard-to-find-36144">Antibiotic-resistant superbugs</a> are on the rise and we’re being urged to forgo antibiotics wherever possible to limit their spread. But serious bacterial infections can only be dealt with effectively using these drugs.</p>
<p>So when should you take antibiotics? The easy answer, of course, is when your doctor tells you to. But there’s more to it. </p>
<p>We know that rates of bacterial resistance track antibiotic usage rates. So, as a community, the more we take these drugs, the more likely we are to have superbugs down the line. And Australia may face a bleak future in these terms.</p>
<h2>Antibiotic myths and facts</h2>
<p>The Australian government’s <a href="http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-amr.htm#tocstrategy">2015-2019 National Antimicrobial Resistance Strategy</a> highlighted some interesting, if somewhat disturbing, facts:</p>
<p>• a 2014 poll of Australian workers showed 65% believed taking antibiotics would help them recover faster from a cold or flu </p>
<p>• 20% of people expect antibiotics for viral infections, such as a cold or the flu </p>
<p>• nearly 60% of GPs surveyed would prescribe antibiotics to meet patient demands or expectations</p>
<p>• surgical prophylaxis (giving antibiotics before or during surgery to minimise the risk of infection) is used in 41% of cases, which is much higher than the recommended best practice of less than 5%.</p>
<p>Clearly, we still don’t understand that antibiotics won’t kill viruses responsible for the flu and many common colds. And a majority of doctors take a seemingly lackadaisical approach to antibiotic stewardship. It’s no surprise then that the <a href="http://www.safetyandquality.gov.au/wp-content/uploads/2014/11/Web-Accessible-2013-NAPS-Report.pdf">2013 National Antimicrobial Prescribing Survey</a> showed 30% of antibiotic prescriptions were inappropriate.</p>
<p>Antibiotics are amazing drugs that can prevent serious harm and stop infections becoming fatal. They’re often used for:</p>
<p>• lung infections, which include bacterial pneumonia and pertussis (whooping cough)</p>
<p>• urinary and genital infections, some of which are sexually transmitted</p>
<p>• eye infections (conjunctivitis)</p>
<p>• ear, nose and throat infections (otitis, sinusitis and pharyngitis)</p>
<p>• skin infections (from impetigo in schoolchildren through to more serious diabetic foot ulcers)</p>
<p>• diarrhoea and more serious gut infections, such as those caused by <em>Clostridium difficile</em>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/93866/original/image-20150904-7025-15uwft5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/93866/original/image-20150904-7025-15uwft5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=440&fit=crop&dpr=1 600w, https://images.theconversation.com/files/93866/original/image-20150904-7025-15uwft5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=440&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/93866/original/image-20150904-7025-15uwft5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=440&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/93866/original/image-20150904-7025-15uwft5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=553&fit=crop&dpr=1 754w, https://images.theconversation.com/files/93866/original/image-20150904-7025-15uwft5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=553&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/93866/original/image-20150904-7025-15uwft5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=553&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antibiotics are often used for serious gut infections, such as those caused by <em>Clostridium difficile</em>.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/frecuenciamedicafb/6866129626/">Francisco Bengoa/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
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<p>In general, a patient will be given antibiotics if her symptoms are severe (a high fever or skin rash, for instance, or inflammation spreading around an infection site); she has a higher risk of complications (such as an elderly patient with suspected pneumonia); or if the infection is persistent.</p>
<h2>Getting it right</h2>
<p>To prescribe, the doctor makes an educated guess as to what may be causing the infection. This is based on knowledge of what type of bacteria are normally found in these cases and, if available, the patient’s history. But she doesn’t know exactly what type of bug is causing the infection. In the absence of an accurate diagnosis, as well as to minimise potential risk to the patient, a broad-spectrum antibiotic is used to “cover as many bases” as possible.</p>
<p>Until we can develop point-of-care technology that can identify a bug on demand, such broad-spectrum drugs (the grenade approach to bacteria) are a better option for doctors than targeted specific drugs (a sniper against superbugs). But the latter is the better long-term option for the patient and the community, although it may not always work.</p>
<p>One key problem with broad-spectrum “grenade” antibiotics is that they can cause collateral damage by killing a lot of good bacteria. We now know that we have about a kilogram and a half of good bacteria in our guts that help us digest food. They also “crowd out” potential nasty infections caused by bad bacteria.</p>
<p>There are cases where patients on antibiotics end up with diarrhoea, <a href="http://www.nhs.uk/Conditions/Thrush/Pages/Causes.aspx">thrush</a> (a vaginal infection caused by <em>Candida</em> that goes wild when protective bacteria are wiped out), or nasty infections, such as <em>Clostridium difficile</em>, that can lead to severe <a href="https://en.wikipedia.org/wiki/Clostridium_difficile_colitis">colitis</a>.</p>
<p>And it gets worse: a <a href="http://press.endocrine.org/doi/pdf/10.1210/jc.2015-2696">recent Danish study</a> that followed more than a million patients found an association between frequency of antibiotic use and Type II diabetes, generating considerable <a href="http://www.dailymail.co.uk/health/article-3213228/Taking-antibiotics-increases-risk-type-2-diabetes-People-just-four-courses-15-years-50-likely-condition.html">media interest</a>. It found people who received more than four courses of the drugs over 15 years were 53% more likely to develop diabetes.</p>
<p>Of course, there’s the cause-effect corollary. People who were already heading towards the disease may simply have been less healthy, more prone to infection, and hence had more visits to the doctor to get antibiotics. The study showed an association between antibiotics and diabetes, not causality.</p>
<p>So where do we stand now? Remember bacterial infections can kill, and antibiotics save lives, so if you’re really feeling crook, go to your doctor and take her advice. But also think twice. If you have a bad cold or think you have the flu, remember this may be due to a viral infection. And using antibiotics could do you more harm than good in the longer term.</p>
<p>The real game changer in all of this will be a “tricorder” diagnostic that can identify a bug on site. With such a technology, a doctor could prescribe the right drug, the first time, in time. So be sensible about using antibiotics and let’s keep our eyes on this <a href="https://longitudeprize.org">prize</a>.</p><img src="https://counter.theconversation.com/content/42751/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Cooper is the Chair of the Scientific Advisory Board of Adenium Biotechnology, a Danish company working on a new antibiotic clinical candidate. He receives funding from the NHMRC, NIH and Wellcome Trust.</span></em></p>Antibiotics can prevent serious harm and stop infections becoming fatal. But they won’t kill common cold and flu viruses, and careless overprescribing by doctors can do more harm than good.Matthew Cooper, Prof. Institute for Molecular Bioscience, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/365552015-07-06T05:09:23Z2015-07-06T05:09:23ZHealth Check: when are we most likely to catch viral diseases?<figure><img src="https://images.theconversation.com/files/87436/original/image-20150706-17494-3qdcz2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Children in particular experience a multitude of viral illnesses during their early years.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/mujitra/12363377564/">MIKI Yoshihito/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Viruses have been described as “organisms at the edge of life”, unable to reproduce outside the cells of those they infect. But this status has not impeded their evolutionary success. Children, in particular, experience a multitude of viral illnesses during their early years, which gradually reduce over time as their natural immunity develops.</p>
<p>Viral infections may be fleeting (think influenza) or chronic (HIV, for instance), affecting various parts of the body to cause a diverse array of symptoms. These differences have important implications for the spread of that particular viral disease. </p>
<h2>Reducing reproduction numbers</h2>
<p>The most relevant factor is the infectiousness of a virus, often summarised in a measure known among epidemiologists as its “reproduction number”. This describes the average number of secondary infections produced by one ill individual. </p>
<p>Consider the most commonly transmitted viral illness, the flu: about 10% to 20% of the population is infected by one of the circulating influenza viruses each year. Symptoms vary from a mild “cold” through to severe respiratory infection requiring hospitalisation.</p>
<p>So it’s perhaps surprising that the reproduction number of influenza is relatively low; <a href="http://www.biomedcentral.com/1471-2334/14/480">each infectious person infects only one and a half other people</a> - or put another way, two infectious people produce, on average, three new cases of influenza. If we could get that reproduction number below one, incidence numbers would decline as, on average, each infected person would not necessarily produce a successor.</p>
<p>What makes the flu difficult to control despite its relatively low reproduction number is the fact that people are <a href="http://www.cdc.gov/flu/about/disease/spread.htm">contagious for a day or two before they show any symptoms</a>. Once they become unwell, they’re contagious for a couple more days. But by this stage they’re more likely to stay home and avoid contact with others. </p>
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<img alt="" src="https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=444&fit=crop&dpr=1 600w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=444&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=444&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=558&fit=crop&dpr=1 754w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=558&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/87430/original/image-20150706-17526-vr24a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=558&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 virus’ ‘reproduction number’ describes the average number of secondary infections produced by one ill individual.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/69382656@N04/6798474143/">FAKEGRIMLOCK/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>As half or more of their secondary infections will have been produced before the ill people showed any symptoms, influenza control strategies that rely on identifying and isolating them aren’t necessarily going to effectively reduce the incidence of the illness in the community. </p>
<p>This incubation period – the time when a person is infected but not showing symptoms – is a vital consideration for controlling viral illness.</p>
<h2>Incubating viruses</h2>
<p>Consider the outbreak of a deadly strain of the coronavirus that caused <a href="http://www.cdc.gov/sars/">Severe Acute Respiratory Syndrome (SARS)</a> in 2003. Like influenza, SARS leads to fever and cough, and is mostly spread by close contact between people. Even though <a href="http://aje.oxfordjournals.org/content/160/6/509.long">its reproduction number</a> has been estimated to be between three and four, people carrying the virus are most contagious in the second week of their infection, after they have started to show symptoms of the disease. </p>
<p>It was this delay until contagion that made it possible to contain SARS: health-care workers were able to find and quarantine people who had contact with the disease before they infected others. Nonetheless, controlling its outbreak was not an easy task – it spread to around 30 countries and killed about 10% of those infected. </p>
<p>SARS appears to have been eradicated but the recently emerged <a href="http://www.cdc.gov/coronavirus/mers/">Middle East Respiratory Syndrome (MERS)</a>, which also belongs to the coronavirus family, has many similarities. The majority of cases, including the <a href="http://www.who.int/csr/don/03-july-2015-mers-korea/en/">recent outbreak in the Republic of Korea</a>, have arisen from infection spread in health-care settings, where early infections are indistinguishable from other respiratory viruses.</p>
<p>Another virus that’s been grabbing news headlines of late is Ebola. While flu and SARS spread through coughing and sneezing, contracting Ebola requires direct contact with the blood or other bodily fluids of an infected person, or with items such as bedding or clothing contaminated with these fluids. </p>
<p>As with SARS, people infected with Ebola are not contagious until they begin to show symptoms, which include diarrhoea, vomiting and bleeding. <a href="http://www.who.int/mediacentre/factsheets/fs103/en/">Contagiousness increases as these symptoms worsen</a> and peaks around the time of death. The body of a deceased person remains contagious after death. Safe burial practices were therefore an <a href="http://www.who.int/mediacentre/news/notes/2014/ebola-burial-protocol/en/">essential component in controlling the recent Ebola outbreak</a>. </p>
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<img alt="" src="https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/87434/original/image-20150706-17496-fvz2ji.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Measles is most infectious in the time between the appearance of non-specific symptoms, such as fever, runny nose and cough, and the development of its classically identifiable rash.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/minnellium/3480352546/">Dave Haygarth/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>The <a href="https://theconversation.com/fast-spreading-killers-how-ebola-compares-with-other-diseases-32944">reproduction number of Ebola</a> in the latest outbreak was as high as four. But, as with SARS, the delay until contagion made it <a href="http://www.cdc.gov/vhf/ebola/outbreaks/what-is-contact-tracing.html">possible to trace and quarantine people</a> who had been in contact with Ebola before they spread the disease any further. </p>
<h2>The importance of vaccines</h2>
<p>In stark contrast to these stories of successful disease control, the <a href="http://www.who.int/hiv/en/">World Health Organisation estimates</a> that 35 million people are living with human immunodeficiency virus (HIV) infection. And more than 39 million have died from the infection to date.</p>
<p>This toll is largely due to the fact that people with HIV infection may take anywhere between two and 15 years to develop symptoms of acquired immune deficiency syndrome (AIDS). Meanwhile, they unknowingly infect others over a period of many years, rather than days or weeks.</p>
<p>HIV spread can be effectively reduced by antiretroviral drugs, which lower virus levels in the blood. Unfortunately, WHO estimates that only a third of the people who need these drugs currently have access to them. Meanwhile, the quest for an HIV vaccine continues. </p>
<p>Vaccines, in fact, are one of the best ways to control the spread of viral illnesses. Consider the numerous childhood illnesses that are now contained thanks to vaccines. </p>
<p>Measles and chicken pox, for instance, are classically identifiable by their distinctive rashes. But they’re most infectious in the time between the appearance of non-specific symptoms, such as fever, runny nose and cough, and the development of this rash. This made it very difficult to control their spread until <a href="http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home">vaccines were developed</a>. </p>
<p>As you can see, different viral diseases are most infectious at different times and this timing of contagiousness plays a key role in how successfully the diseases spread. Knowing a virus’ most infectious period is vital for working out the kinds of measures that are likely to work to control and perhaps even eradicate it from the community.</p><img src="https://counter.theconversation.com/content/36555/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jodie McVernon receives funding from the Australian Government Department of Health, the Australian Research Council and the National Health and Medical Research Council (NHMRC). She leads an NHMRC funded Centre of Research Excellence in Infectious Disease Modelling to Inform Policy, on which all co-authors are co-investigators. She is a member of the Australian Technical Advisory Group on Immunisation and a Director of the Influenza Specialist Group. </span></em></p><p class="fine-print"><em><span>James McCaw receives funding from the ARC and the NHMRC.</span></em></p><p class="fine-print"><em><span>Joshua Ross receives funding from the Australian Research Council and the National Health and Medical Research Council.</span></em></p><p class="fine-print"><em><span>Kathryn Glass receives funding from the ARC and the NHMRC.</span></em></p><p class="fine-print"><em><span>Nicholas Geard receives funding from the Australian Research Council and the National Health and Medical Research Council.</span></em></p>Viruses cause all kinds of infections from relatively mild cases of the flu to deadly outbreaks of Ebola. Clearly, not all viruses are equal and one of these differences is when you can infect others.Jodie McVernon, Associate Professor, Population Health, The University of MelbourneJames McCaw, Associate Professor in Mathematical Biology, The University of MelbourneJoshua Ross, Associate Professor in Applied Mathematics, University of AdelaideKathryn Glass, Fellow, Australian National UniversityNic Geard, ARC DECRA Research Fellow, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/351512014-12-09T11:08:07Z2014-12-09T11:08:07ZEven with mismatches flu shots can still keep you from getting sick<figure><img src="https://images.theconversation.com/files/66633/original/image-20141208-5168-ggrpk6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There is no such thing as an ideal flu shot. But that doesn't mean you should skip it.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&searchterm=flu%20shot&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=230545201">Sherry Yates Young/Shutterstock</a></span></figcaption></figure><p>On December 3, the US Centers for Disease Control and Prevention (CDC) issued a Health Alert Network <a href="http://emergency.cdc.gov/HAN/han00374.asp">advisory</a> indicating a possible strain mismatch in this year’s vaccine. After the usual brief flurry of media attention, it is worth examining what this really means for the general public and health-care providers. </p>
<p>First, let’s be realistic about influenza vaccines: none are perfect when it comes to protection. Some people who receive a vaccine will still get influenza. This is because protection is not just about what’s in the vaccine – it’s also heavily dependent on the individual. For instance, vaccine benefit is greatest in those with a healthy immune system. </p>
<p>Timing is also important. Getting the vaccine well before influenza starts circulating is crucial because it takes an individual at least a couple of weeks to develop full immunity. Having a flu shot in the morning won’t protect you from the sick person sitting beside you in the doctor’s clinic this afternoon. </p>
<p>There is also subtle variation in the protection afforded by the different types of vaccines: three-strain formulations vs four strains; regular vs high-dose; nasal sprays vs shots. Getting confused yet? And finally, the circulating strains of influenza should ideally match what is in the seasonal shot. But, flu strains can and do change.</p>
<p>Given so much vaccine complexity, and the innate ability of influenza viruses to change over time, the protection is never 100%. We typically average <a href="http://www.cdc.gov/flu/about/qa/vaccineeffect.htm">about 60%</a> in a good year. Remember that doesn’t mean 40% of vaccinated people will get sick. It means 60% of those people who might have got sick without the vaccine stayed healthy. In a really busy flu season, that means a tremendous number of people benefit from the vaccine. </p>
<h2>A ‘drifting’ and ‘shifting’ virus</h2>
<p>Current influenza vaccines contain either three of four different strains: two Influenza A strains (H1N1 and H3N2) and one or two Influenza B strains. Typically, A-strains are not only more common, but more likely to cause severe disease. Usually two A-strains circulate together at any given time and predicting which ones will be predominant in a given season can be a difficult science.</p>
<p>It would be easy if influenza didn’t naturally mutate – what was here last year will be here again. This year the H3N2 strain, which has been predominant, has mutated. Influenza is prone to <a href="http://www.cdc.gov/flu/about/viruses/change.htm">both</a> “drifting” and “shifting”. Drifting occurs most years, leading to subtle genetic changes that allow the virus to better evade our immune systems. This is a more gradual process.</p>
<p>Shifting, where the virus makes a sudden change, is a rare occurrence. An enormous shift can result in widespread infection, because people’s immune systems have little or no collective memory of the virus. The H1N1 strain behind the <a href="http://www.cdc.gov/flu/spotlights/pandemic-global-estimates.htm">2009 pandemic</a> is a typical example. </p>
<p>Adding to the complexity is the vaccine manufacturing process, which is painfully slow. Influenza modeling teams gather in February to predict which strains will circulate the following winter, allowing enough time to put vaccines into production in sufficient number. That leaves more than six months for strains to significantly drift, as occurred this year.</p>
<h2>A mismatch isn’t all bad news</h2>
<p>Many people vaccinated with a mismatched flu shot will still mount a perfectly appropriate response and clear an infection, thanks to cross-reactivity between strains. Basically, what this means is that the mismatched flu vaccine can still be effective because those strains that have changed are still related to the ones the vaccine protects against.</p>
<p>Despite all the complexity, there is little statistical evidence that a mismatch with one strain is all that bad. We can still expect to be well protected against the other Influenza A strain (H1N1) as well as the Influenza B strains. Furthermore, even if a drift in the Influenza A H3N2 strain leaves more people prone to infection, vaccination efficacy in badly matched years still approaches <a href="http://www.biomedcentral.com/1741-7015/11/153">50%.</a> Put another way, because of the vaccine almost half of the potentially infected individuals will not contract the flu. And we typically expect an infected patient with influenza to spread the virus to up to three additional people, so even a mismatched vaccine shields people from flu and can have meaningful impact on community health.</p>
<p>We know there isn’t a perfect flu vaccine available, so we still need to be cautious about personal hygiene and aggressively treat flu when it occurs. We also have outstanding evidence of vaccine safety when it comes to modern influenza vaccines. That data, combined with the knowledge that even a mismatched vaccine still affords great community benefit, should mean that the ultimate message we get from the CDC Health Alert is to continue vaccinating.</p><img src="https://counter.theconversation.com/content/35151/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Cameron R. Wolfe receives funding from the NIH to conduct research into new influenza treatments.</span></em></p>On December 3, the US Centers for Disease Control and Prevention (CDC) issued a Health Alert Network advisory indicating a possible strain mismatch in this year’s vaccine. After the usual brief flurry…Cameron R Wolfe, Assistant Professor of Medicine, Duke UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/255622014-04-24T12:01:08Z2014-04-24T12:01:08ZGinseng could be an effective way to prevent the flu<figure><img src="https://images.theconversation.com/files/46936/original/nwcmjm6q-1398264742.jpg?ixlib=rb-1.1.0&rect=0%2C515%2C683%2C437&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Flavour is another thing.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/53766310@N02/6139690868/sizes/l">Florina_Presse</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Ginseng, the root of the plant <em>Panax ginseng</em>, is one of the most commonly used herbal medicines and is often sold as an over-the-counter remedy for fatigue. Although it has been used by humans for thousands of years, more recent research has begun to investigate therapeutic and pharmacological uses including <a href="http://www.ncbi.nlm.nih.gov/pubmed/22360884">anti-allergy</a> and <a href="http://www.ncbi.nlm.nih.gov/pubmed/21494373">anti-inflammatory properties</a>. It is also known to act on the immune system and to affect viral replication. And it may also be a very effective way of preventing the flu.</p>
<p>The findings of a recent study we carried out suggest that normal consumption of Korean red ginseng extract by healthy individuals could prevent infections by different flu virus strains. And studies in mice suggest that long-term ginseng intake could confer and prepare immune systems with better resistance to fight future pathogens. </p>
<p>The effect that ginseng has on flu virus infections regardless of strain makes it different from the <a href="https://theconversation.com/a-universal-flu-vaccine-is-still-some-time-off-18525">strain-specific protection</a> from annual vaccinations (often given to those most at risk such as the elderly and pregnant women, and <a href="http://www.nhs.uk/Conditions/vaccinations/Pages/how-flu-vaccine-works.aspx">determined by the strains in most circulation</a> in a given year) and prescribed antiviral drugs such as Tamiflu – which <a href="http://www.nhs.uk/news/2014/04April/Pages/questions-over-tamiflu-relenza-effectiveness.aspx">recently came under fire</a> over its effectiveness as a treatment against severe flu.</p>
<h2>Rooting around</h2>
<p>Korean red ginseng extracts are produced by steaming and drying the fresh roots of six-year-old <em>Panax ginseng</em> plants. These are then boiled in water and the supernatants – or liquids above the settled material – are concentrated. It is this preparation that can be designated as “red ginseng extract.” Because of its prominent biological effects, extracts from this particular plant have been used in animal studies. Despite known beneficial effects on human health and its action on viral infection, the mechanism for how it does this remains largely unknown. </p>
<p>In <a href="http://www.ncbi.nlm.nih.gov/pubmed/22856395">previous studies</a>, we investigated the effects of ginseng given orally in mice – the most common way that healthy people take ginseng as a supplement. We found that this gave the mice a moderate but significant resistance to infection with the 2009 pandemic flu virus strain – on the whole it didn’t prevent illness, which was shown by them losing weight, but it did result in better survival.</p>
<p>Protection from ginseng given before infection wasn’t strong because the mice still became ill but we also found that treating them with ginseng after infection gave even less protection.</p>
<h2>Cross-protection</h2>
<p>However most human adults who consume ginseng already have some immunity to the flu, either through previous contact with the virus or vaccination. So we tried giving ginseng instead to vaccinated mice instead through oral doses and found that it significantly improved how well the mice were able to fight different strains of flu viruses through cross-protection.</p>
<p>Infection of mice with a mixture of influenza virus and ginseng extract resulted in better clearance of lung viral levels and lower levels of inflammatory cytokines, the small proteins that are important in helping cells to send signals. But it also led to higher levels of antiviral cytokines. From these lab tests we know that Korean red ginseng extract may inhibit the flu virus growing. The extract appears to have multiple mechanisms against fighting infectious diseases, which might be beneficial if taken in healthy mice with previous exposure and prior to infections.</p>
<p>Our more recent study, <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942714/">published in Nutrients</a> found that ginseng improved the survival of human lung epithelial cells (tissue cells that line cavities in the lung) when someone is infected with the flu virus. Also, ginseng treatment reduced the expression of pro-inflammatory genes, probably in part by interfering with chemically reactive molecules that contain oxygen and which are formed by the flu virus.</p>
<p>Taking ginseng for a longer term (around 60 days) showed multiple effects on the immune system of mice such as stimulating anti-viral protein production after flu virus infection. Ginseng also inhibited the infiltration of inflammatory cells into the lungs in mice. So ginseng might have potential beneficial effects in preventing flu virus infections by acting on the immune system in multiple ways. </p>
<p>Small doses of ginseng has been taken in humans for many years with no major side effects. But while ginseng looks like a promising way to help prevent flu, results only relate to healthy individuals taking normal doses. Based on animal studies it also has shown no or only minimal protective beneficial effects if treated after the onset of symptoms. </p><img src="https://counter.theconversation.com/content/25562/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sang-Moo Kang has received funding from NIH/NIAID grants and the Korean Ginseng Corporation for his research</span></em></p>Ginseng, the root of the plant Panax ginseng, is one of the most commonly used herbal medicines and is often sold as an over-the-counter remedy for fatigue. Although it has been used by humans for thousands…Sang-Moo Kang, Associate Professor, Institute for Biomedical Sciences, Georgia State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/235772014-02-28T18:22:20Z2014-02-28T18:22:20ZScientists create accurate predictor of the next flu virus<figure><img src="https://images.theconversation.com/files/42764/original/w9947w2f-1393601811.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">That crystal ball we ordered? New flu model helps predict future strains.</span> <span class="attribution"><a class="source" href="http://www.flickr.com/photos/april-mo/11188822274/sizes/l/">April Mo</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Influenza viruses rapidly evolve in shape, making it hard to develop protective vaccines against them. Despite a great deal of study, scientists have been at a loss to forecast their evolution in any detail for decades. Now, thanks to improvements in our ability to study viruses and a new mathematical model, anticipating influenza’s next move <a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13087.html">appears possible</a>.</p>
<h2>Making the jump</h2>
<p>Influenza presents two kinds of evolutionary challenges. One is its ability to jump from animals to humans and spark global pandemics, for example swine flu <a href="http://www.theguardian.com/uk/interactive/2009/may/05/swine-flu-cases-britain">which killed thousands from Mexico to China in 2009</a>.</p>
<p>But a pandemic does not always follow from these jumps. For example there have been reports of humans being infected with the H5N1 bird flu, without it spreading en masse. Researchers are still trying to understand the reason why some influenza viruses are unable to spread, while others have taken off.</p>
<h2>Year to year</h2>
<p>One of the successful jumps was made in 1968 <a href="http://wwwnc.cdc.gov/eid/article/12/1/pdfs/05-1254.pdf">by a subtype called H3N2</a>. H3N2 evolves quickly enough that its entire population is replaced every few years. It exemplifies the second type of evolutionary challenge: predicting, from year to year, which of the many circulating strains will take over. </p>
<p>Because influenza is a major cause of death as a result of pneumonia, understanding this evolution is more than an academic exercise. Predicting which strain will be widespread nearly a year into the future is the central challenge of the World Health Organisation’s vaccine strain selection committee. It meets twice a year to review the evidence on circulating viruses and pick the likeliest candidates for the next flu seasons.</p>
<p>The problem is that it is difficult to build a compelling case against any one strain. Influenza’s rapid evolution in humans is partly driven by its fight to survive against our immune systems. Viruses with mutations that allow them to escape antibodies tend to spread faster, leaving a trail of immunity that helps drive their weaker ancestors to extinction.</p>
<h2>Slow and costly</h2>
<p>But measuring how well different strains have escaped immunity has been a slow and costly science. Traditionally, ferrets are experimentally infected with common strains to see how well they develop antibodies that react with the candidate vaccine strains. These are then compared with measures from human samples. Often, several strains show some ability to escape immunity.</p>
<p>For more than a decade, different groups have attempted to find genetic shortcuts to predict the winners in advance. Influenza researchers have long known that mutations in certain parts of the virus are more likely to lead to immune escape than others. But in the past, every time a rule was derived, the virus seemed to break it. </p>
<p>Over time, however, this pattern gradually enforced a recurring theme in evolution: the impact of a mutation depends heavily on the genetic background in which it occurs. For fast-evolving viruses such as influenza, the combinatorial possibilities of mutations and backgrounds has made prediction seem like a daunting task.</p>
<h2>A new model</h2>
<p>But a recent study published in Nature shows that, in the case of H3N2, we perhaps can predict its evolution after all. The study authors, Marta Łuksza and Michael Lässig, showed that the future success of related H3N2 strains, known as clades, could be predicted by a relatively simple model. </p>
<p>The model considers only three types of information when assessing a clade’s future: mutations in sites that bind antibodies (generally thought to be beneficial), mutations in sites not binding antibodies (generally thought to be harmful), and the recent frequencies of the clade and competing clades. Most powerfully, the authors showed the model can be used to predict strain frequencies on a time scale useful for creating vaccines. This could greatly increase the effectiveness of flu jabs in protecting against the virus.</p>
<p>In addition to its ability to select strains, the model also reveals important information about the way influenza evolves. The immunity acquired by host populations from infections with different strains shapes the virus’ evolution. This suggests that widespread vaccination could shape the evolution of influenza. </p>
<p>The study also contributes evidence to the idea that strains emerging from Asia tend to be <a href="http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000918">inordinately successful</a>. Why this is, and whether the trend will continue, are unanswered questions. Finally, the model reveals that as it evolves, influenza follows a narrow path between beneficial mutations to escape immunity and harmful ones that affect its functional stability.</p>
<p>How do we know the virus won’t break the rules of this model too? In a way, we don’t, but the authors took steps to show that their model balanced the trade off between complexity and predictive power. Their ability to find this sweet spot comes entirely from the large and growing number of publicly available influenza sequences. It gives hope that other evolutionary challenge, such as predicting whether H5N1 or H7N9 might make the jump, could be solvable too.</p><img src="https://counter.theconversation.com/content/23577/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Cobey 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>Influenza viruses rapidly evolve in shape, making it hard to develop protective vaccines against them. Despite a great deal of study, scientists have been at a loss to forecast their evolution in any detail…Sarah Cobey, Assistant Professor of Ecology & Evolution, University of ChicagoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/139202013-08-22T05:47:50Z2013-08-22T05:47:50ZAvian flu may have moved between humans but we’re still far from a pandemic<figure><img src="https://images.theconversation.com/files/28864/original/zkskzmny-1375889677.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1024%2C691&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Viral workload: how did H7N9 make the human-to-human leap?</span> <span class="attribution"><span class="source">James Gathany</span></span></figcaption></figure><p>The H7N9 virus is thought <a href="http://www.telegraph.co.uk/health/flu/10226810/Deadly-avian-flu-spreads-person-to-person-for-first-time.html">to have been transmitted between</a> a 60-year-old man in China and his 32-year-old daughter, who cared for him. Experts said she had been previously healthy and, unlike her father, had no known exposure to live poultry before falling ill. Both were reportedly treated in intensive care but died of multiple organ failure.</p>
<p>The new H7N9 influenza virus emerged in China in spring 2013. In the first month, the virus infected more than 100 people and was lethal in a fifth of cases. By July, <a href="http://www.who.int/csr/don/2013_07_20/en/index.html">134 cases and 43 deaths</a> had been reported.</p>
<p>Chickens, pigeons and environmental samples taken from live poultry markets in the affected area tested positive, which suggested them as a source of infection. H7N9 had never before circulated in humans but all 7bn or so of us are fully susceptible to it. Until now, however, the virus didn’t transmit between humans because it hadn’t acquired the right adaptive mutations. </p>
<p>It’s a worrying development, <a href="http://bit.ly/17340RR">but experts have said</a> the virus’ ability to transmit itself is “limited and non-sustainable”. </p>
<h2>Making a leap</h2>
<p>Viruses are tiny microbiological entities that are not independently alive but rely on gaining access to a living cell for survival. They interact intimately with cellular machinery, subverting it for their own ends to amplify hundreds of copies of their viral genetic material and then use virally encoded protein shells called capsids to move their genomes onto the next host. </p>
<p>Viruses are usually specialists at infecting a particular type of cell inside a specific host, because they have co-evolved with that species and the viral proteins are a good fit with those of the host. Take influenza as an example; natural host species are wild aquatic birds. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/28865/original/v6cmgx8v-1375890122.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/28865/original/v6cmgx8v-1375890122.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=766&fit=crop&dpr=1 600w, https://images.theconversation.com/files/28865/original/v6cmgx8v-1375890122.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=766&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/28865/original/v6cmgx8v-1375890122.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=766&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/28865/original/v6cmgx8v-1375890122.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=962&fit=crop&dpr=1 754w, https://images.theconversation.com/files/28865/original/v6cmgx8v-1375890122.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=962&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/28865/original/v6cmgx8v-1375890122.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=962&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Not so cute now.</span>
<span class="attribution"><span class="source">David Monniaux</span></span>
</figcaption>
</figure>
<p>Occasionally, an influenza virus passes from ducks to poultry, or to other domesticated animals such as pigs or horses, or even to humans. This is called zoonosis. </p>
<p>But if the zoonotic virus manages to undergo some replication, mutations that work better with the new host can adapt the virus to its new environment. This basic Darwinian evolution happens very quickly for viruses compared to larger organisms because viruses copy vast numbers of genomes and often replicate their genetic material without proof reading the results first.</p>
<h2>Breaking through barriers</h2>
<p>Research accumulated over a number of years has suggested at least two barriers that restrict avian influenza viruses in humans: the avian flu viruses bind poorly to human cells, and the virus would have to “switch” to do be able to go from human to human. </p>
<p>Viruses that caused influenza pandemics in 1957 and 1968 were able to make two mutations in order to switch. Interestingly, the current H7N9 viruses have one but not both of these changes. This may explain the ability of the virus to more frequently infect exposed humans than previous H7 avian viruses. </p>
<p>That the H7N9 virus doesn’t have two of these mutations may be why it still won’t efficiently transmit between humans, and likely why the Chinese researchers believe the virus that infected the father and daughter is “limited and non-sustainable”.</p>
<p>The second barrier avian influenza viruses must overcome to infect human cells is the poor performance of a virally encoded enzyme whose job it is to interact with the nucleus of the infected cell and direct the replication of the virus’ genome. However, it’s readily overcome if the genes that encode the enzyme mutate. One gene in particular, PB2, has already been shown to have mutated in humans but not birds.</p>
<p>Taken together, the H7N9 mutations place it one step closer to human-to-human transmission <a href="https://theconversation.com/severity-of-h7n9-compared-to-other-flu-outbreaks-15487">than the notorious H5</a> virus around since 2003.</p>
<h2>Final piece of evolution?</h2>
<p>In research into H5N1, in which artificial viruses were created and transmitted between ferrets, it was discovered that one other mutation in the HA protein enabled the virus to transmit through the air, by making it more resistant to heat or low pH. </p>
<p>It’s conceivable that this is the final piece of evolution required to achieve transmission in humans; a mutation that enhances survival so that the virus reaches the new host intact, despite the harsh environmental exposure it undergoes during the transmission process. And how readily H7 or any other emerging influenza virus can acquire this property may be what determines the next influenza pandemic.</p>
<p>This research may also reveal important clues about the likelihood that other emerging pathogens <a href="http://www.bbc.co.uk/news/health-23179564">such as the new coronavirus</a> could cause new epidemics. Work involving poliovirus, a completely different virus that enters through the mouth, has recently identified that stability of the virus particle is enhanced by interaction with bacteria in the gut and this is key to its onwards transmission. </p>
<p>In the end a virus can only continue to exist if it can pass from one host to the next. Emergence of new pandemics is largely driven by transmissibility and understanding this process is now, quite rightly, an intense area of research.</p><img src="https://counter.theconversation.com/content/13920/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Wendy Barclay's laboratory is funded by the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the Wellcome Trust and commercial bodies.</span></em></p>The H7N9 virus is thought to have been transmitted between a 60-year-old man in China and his 32-year-old daughter, who cared for him. Experts said she had been previously healthy and, unlike her father…Wendy Barclay, Professor of Virology , Imperial College LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/148152013-06-04T01:19:54Z2013-06-04T01:19:54ZH1N1, H5N1, H7N9? What on earth does it all mean<figure><img src="https://images.theconversation.com/files/24970/original/jhyvpc9t-1370302448.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">One of three major types of the flu viruses that infect people, influenza A ranges from H1 to H17 and from N1 to N9.</span> <span class="attribution"><span class="source">Señor Codo</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - Ever wondered what flu classifications mean? Read on.</em></p>
<p>The pandemic influenza strain, or swine flu, that spread globally in 2009 was referred to as H1N1 and the <a href="http://www.who.int/csr/don/2013_05_29/en/index.html">new bird flu</a> currently spreading in China is A H7N9. Most of us can probably understand what is meant by bird or swine in this context but what do the letters and numbers mean?</p>
<p>There are three major types of influenza that infect humans, known as influenza A, B and C. Influenza A and B can both cause serious infections, and are the cause of what we call the flu. Influenza C viruses differ from influenza A and B, and only cause a mild infection, so they don’t appear in vaccines. </p>
<p>A pandemic influenza strain is one that humans have not been previously exposed to, so people do not have immunity to it. It also spreads rapidly in the community. </p>
<p>When it has been around for a while and there’s widespread immunity to it, the virus will cause less serious illness, becoming one of the annual seasonal strains. But these seasonal strains continue to change all the time, never going back to the original strain.</p>
<h2>Hs and Ns</h2>
<p>Influenza A and B viruses have two types of spikes that cover their surface – the haemagglutinin (H) and the neuraminidase (N). </p>
<p>Viruses attach by their haemagglutinin onto receptors on the surface of cells in order to infect them, like a grappling hook. And the neuraminidase removes these receptors from infected cells at the right time to allow newly synthesised viruses to escape and spread.</p>
<p>Among influenza A viruses there are 17 different types of haemagglutinin, from H1 to H17 and nine different types of neuraminidase, from N1 to N9. Each virus has one type of H (such as H1) and one type of N (such as N1).</p>
<p>While most strains of influenza A viruses infect multiple types of birds, including poultry, ducks and geese, some strains also infect pigs. Indeed, avian influenza strains are endemic in wild birds, especially in Asia. But, interestingly, most birds don’t get ill from the flu.</p>
<p>The new H7N9 strain emerging in China does not make birds ill, for instance, but has been killing about a third of infected humans. The H5N1 strain, on the other, has evolved to kill birds and some humans who are infected from these birds. </p>
<p>So, while there are many combinations of H and N seen in birds, widespread human infection has only been caused by a few. H1N1, which was responsible for the 1918 pandemic virus and the recent swine flu pandemic, H2N2, the 1957 Asian flu pandemic strain, and the H3N2 Hong Kong pandemic strain in 1968, which displaced the Asian flu.</p>
<p>The seasonal influenza A strains currently circulating in humans are H1N1 and H3N2, but they have changed a lot since their first introduction into humans. </p>
<p>Influenza B strains do not circulate in animals, so they cannot cause a pandemic. But, like influenza A viruses, they continually change, so we will never become immune to every strain. These are the other component of the flu vaccine.</p>
<h2>Immune responses</h2>
<p>When we are infected with a virus, or given an influenza vaccine (the flu shot), we mount an immune response. Antibodies against this virus will continue to circulate in our bodies, and will help prevent future infection with the same strain of virus if we are exposed to it again.</p>
<p>Although seasonal “flu shots” contain H1N1, H3N2 and influenza B viruses, the strains are selected from the viruses circulating at the end of the spring the previous year. But there are continual changes (from year to year) within each strain.</p>
<p>This means that even if you were infected or vaccinated with the strains of flu circulating last year, when the virus comes around this year, it may have changed sufficiently so your antibodies no longer recognise it. So you can still get flu, even if you have been vaccinated.</p>
<p>While H5N1 and H7N9 strains can directly infect humans from birds, these viruses have not yet adapted sufficiently to spread from human to human. They could adapt either through random mutations, or by generating a mixed or “reassortant” virus.</p>
<p>This happens if two different strains of influenza infect the one host. They can swap and mix their genes, and may generate a virus that can now spread from human to human.</p>
<p>Vaccines can be used to prevent flu, but it’s critical to have the matching H and N to provide immunity. When a new pandemic strain arises, such as the H5N1 or H7N9, we don’t have vaccines against that unique combination of H and N.</p>
<p>It can take more than six months to make a vaccine against a virus with new combination of H and N types, so those of us who work on influenza hold our breath when there are reports of numerous people being infected with a new bird or animal strain. Who knows what numbers of the dice will be our next pandemic strain?</p>
<p><em>This is the third article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14815/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer McKimm-Breschkin 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>Facts about Flu - Ever wondered what flu classifications mean? Read on. The pandemic influenza strain, or swine flu, that spread globally in 2009 was referred to as H1N1 and the new bird flu currently…Jennifer McKimm-Breschkin, Chief Research Scientist, Virology Project Leader, CSIROLicensed as Creative Commons – attribution, no derivatives.