Coronavirus aggressively invades lung cells in chilling new images
The images were published in the New England Journal of Medicine and show how prolific coronavirus can become in a mere four days.
10 September, 2020
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<p>Even cast sterile monochrome, the pictures are spine shivering. At first blush, they appear to depict some unknown fungus devouring a sea anemone or maybe spider egg sacs infesting some poor soul's hair. But the actual subject is far too familiar these days. <a href="https://bigthink.com/tag/coronavirus" target="_self">Those pictures show novel coronavirus</a> in the microscopic flesh.</p><p><a href="https://www.nejm.org/doi/full/10.1056/NEJMicm2023328" target="_blank" rel="noopener noreferrer">Published in the New England Journal of Medicine</a>, the images offer an up-close and far-too-personal look at lung cells teeming with coronavirus. They were produced by Camille Ehre, an assistant professor at the University of School of Medicine's Marsico Lung Institute, and her team. They wanted to research how coronavirus occupied human airways and what happened to the inundated cells. And they vividly got their answer.</p>
Not exactly camera shy
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzg2MjU2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0MDcyMzY5N30.P9-pN3720tOzXNrYTybx3X7qc_7ZO8ZdF15ztj5cgXA/img.jpg?width=1245&coordinates=0%2C52%2C0%2C68&height=700" id="9dbf0" class="rm-shortcode" data-rm-shortcode-id="dd5152d7ead13cca82f0f19be988f538" data-rm-shortcode-name="rebelmouse-image" />Another image of novel coronavirus. This one shows the virions 10 times closer than the above image.
<p>To start, Ehre and her team exposed epithelial cells to novel coronavirus in a biosafe laboratory. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457445/" target="_blank" rel="noopener noreferrer">Epithelium tissues</a> are found at the barriers between the human body and the outside world, often lining the outer surfaces of organs and blood vessels. They serve many functions, including protection, fluid balance, particle clearance, and triggering immune responses. These functions make them important to the health and safety of our respiratory system.</p><p>The researchers took their epithelial cells from a bronchus, major airway passages by which air moves from the windpipe and into the lungs. The initial cells were taken from a transplanted lung and later grown in lab dishes. So, unlike your typical photoshoot or family portrait, this experiment remained ethically above board.</p><p>After exposing the cells to coronavirus, they waited for the infection to take hold. They then captured images of the epithelial cells with a <a href="https://serc.carleton.edu/research_education/geochemsheets/techniques/SEM.html" target="_blank" rel="noopener noreferrer">scanning electron microscope</a>, a device that uses a focused beam of high-energy electrons to produce images. They discovered a high density of virions—individual particles of the virus existing outside the host cell—had been produced and were swarming over the cells. In a mere 96 hours, virus production skyrocketed to reach a multiplicity of infection of three to one. That means there were three virions for each targeted airway cell.</p><p>"When we looked at these infected cultures under an SEM microscope, the most striking observation was the astonishing number of virions produced by a single infected cell," <a href="https://gizmodo.com/horrifying-images-show-how-the-coronavirus-ravages-our-1844946904" target="_blank" rel="noopener noreferrer">Ehre told Gizmodo in an interview</a>. "Some of these infected cells were so engorged with viruses that they rounded up and detached from the epithelium, giving the impression that they were about to burst."</p><p>The image at the top of this article shows the invasion at one-micrometer magnification. The tentacle-looking projections are <a href="https://medlineplus.gov/ency/imagepages/19533.htm#:~:text=The%20bronchus%20in%20the%20lungs,the%20bronchus%20and%20trap%20microorganisms" target="_blank" rel="noopener noreferrer">respiratory cilia</a>, hair-like organelles on epithelium that move microbes and other debris out of our airways. That spider-web looking stuff is mucus produced by goblet cells; it's used to trap microorganisms and protect the bronchus. Neither are effective against the locust-like plight of virions.</p><p>Above is the same scene but at 100 nanometers (10 times closer). From this all-too intimate vantage, you can clearly see <a href="https://www.oxfordreference.com/view/10.1093/oi/authority.20110803100316752" target="_blank" rel="noopener noreferrer">the peplomers</a>—those spiky protrusions on the virions' envelopes. These peplomers give the coronavirus family its name as they have <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus" target="_blank" rel="noopener noreferrer">a crown-like appearance</a> when viewed under such a high magnification—<a href="https://www.dictionary.com/browse/corona?s=ts" target="_blank" rel="noopener noreferrer"><em>corona</em></a> coming from the Latin for "garland or crown."</p>Protect your lungs, wash those hands
<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="9626d989ee28bca36e49da0bbbc6c064"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/deJ3nZhK8KI?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>These images are a stark reminder of why COVID-19 infections can so devastate the human body. It's not only that our bodies serve as their viral birthing centers. It's that we're their all-in-one resource smorgasbord.</p><p>Because <a href="https://www.genome.gov/genetics-glossary/Virus" target="_blank" rel="noopener noreferrer">viruses can't reproduce on their own</a>, they have to inject their genetic material into host cells. They incorporate their DNA or RNA into a host cell's genome, and a bouncing baby virion is born, one that often kills the host upon release. It's basically the backstory of "<a href="https://www.imdb.com/title/tt0090605/?ref_=fn_al_tt_1" target="_blank" rel="noopener noreferrer" style="">Aliens</a>" at a Lilliputian scale, and should viral proliferation spread too quickly, even our immune-responsive Marines can't put up a fight. If enough cells are destroyed, the harm can affect the entire host organism—which now includes us.</p><p>"These images of SARS-CoV-2 infected cultures showing ciliated cells jam-packed with viruses releasing large clumps of virus particles make a strong case for the use of masks by infected and uninfected individuals to limit SARS-CoV-2 transmission," Ehre said.</p><p>They certainly do. Warnings about coronavirus in the abstract can make the case for physical distancing, shuttered schools, and wearing stifling makes while shopping. For a while. But as we've seen, people will eventually tire of their social sacrifices. Perhaps the idea of the above horror show occurring more closely to home will spur us to keep up the fight and listen to the experts for a while longer.</p>
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Study shows why face shields don’t work as well as face masks
Some people choose alternatives to masks for comfort. A study shows the difference in effectiveness.
03 September, 2020
Credit: Siddhartha Verma, Manhar Dhanak, John Frankenfield
- A new study provides a visualization of why face shields are ineffective at stopping the spread of COVID-19.
- Using a mannequin that could simulate coughing, the authors demonstrated how water droplets slide around shields.
- The authors conclude that shields are not an effective replacement for masks.
<p>Face masks are everywhere these days, and for very good reason. They are proven to help reduce the chance of spreading COVID-19 by limiting how far water droplets people <a href="https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-mask/art-20485449" target="_blank">exhale can go,</a> and most establishments won't let you in without one. Despite this, complaints about wearing them abound. </p><p>A common and all too human one is that they prevent people from seeing your facial expressions, a key element of human communication. Others protest that masks are uncomfortable, and people who need glasses are quick to tell you that masks often cause glasses to fog. Many have tried using face shields, large plastic screens, in place of a proper mask to avoid these issues.</p><p>While the CDC already stated that face shields are not recommended as a replacement for <a href="https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-cover-guidance.html#masks-with-vents" rel="noopener noreferrer" target="_blank">face masks</a>, a new study offers a visualization of the price you pay in protection in exchange or an ounce of comfort. </p>
A cool, if slightly terrifying, visualization.
<p>The straightforwardly named "<a href="https://aip.scitation.org/doi/pdf/10.1063/5.0022968" target="_blank"><em>Visualizing droplet dispersal for face shields and masks with exhalation valves</em></a><em>" </em>was published in the journal "<a href="https://aip.scitation.org/journal/phf" target="_blank">Physics of Fluids</a>" and led by Dr. Siddhartha Verma of Florida Atlantic University. In it, the researchers explain that while face shields are very good at blocking the forward motion of larger droplets of water, the large open space in their design allows for smaller droplets to pass them and disperse throughout the room, reducing their potential benefits.</p><p>The authors attached a face shield to a slightly modified mannequin that could simulate coughing to demonstrate this. Small droplets of water and glycerin, comparable in size to the lower end of estimates of what is needed for a virus to travel, were blown through the mannequin's mouth and highlighted with laser sheets as they traveled throughout the room. </p> As illustrated below, small droplets that stop moving forward do not immediately drop to the floor, but instead, they float toward the gap at the bottom of the shield. Following air currents, the droplets eventually made their way around the face shield and began to spread. Given enough time, they'll spread up to a few feet away.<iframe width="750" height="423" src="https://www.youtube.com/embed/JEy1cF2pMdM" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><p>Dr. Verma explained the weaknesses of face shields to the <a href="https://www.nytimes.com/2020/09/01/well/live/face-shields-masks-valves-vents.html" target="_blank">New York Times</a>:</p><p>"Masks act as filters and actually capture the droplets and any other particles we expel. Shields are not able to do that. If the droplets are large they will be stopped by the plastic shield. But if they are aerosol sized, 10 microns or smaller, they'll just escape from the sides or the bottom of the shield. Everything that is expelled will very likely get distributed in the room."</p><p>The authors note that the water droplets' concentration is reduced by wearing a face shield, meaning that fewer droplets are spread than would be spread by a person without any protection. The benefits of this are limited, though, and a previous study carried out by the authors of this test also shows how much more effective proper face masks are than face <a href="https://aip.scitation.org/doi/10.1063/5.0016018" target="_blank">shields</a>. Another study from 2014 gives face shields a mere 23 percent efficiency at reducing the inhalation of such <a href="https://www.tandfonline.com/doi/full/10.1080/15459624.2013.877591" target="_blank" rel="noopener noreferrer">droplets</a>. </p><p>It should be no surprise, then, that the study concludes that face masks are preferable to face shields when it comes to slowing the spread of COVID-19.</p><p>The study also considered face masks with exhaust values, as shown in the final test in the above video. Face masks with exhaust values allow unfiltered droplets to go through the valve. Why they don't do much to prevent droplets from spreading everywhere is obvious. Just as with face shields, the droplets that are initially unable to move forward eventually manage to get to the same place through dispersion. </p>
Why you should wear a proper facemask, revisited.
<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="232361a0d3ad7a620c9ad6d8eec8fa50"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/UFX9oS2kpUA?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>The shortcomings of face shields and other mask alternatives are not shared by the thing they are meant to replace, the basic, well-made face mask.</p><p>As explained above, face masks work to keep others around you from getting your germs by keeping the water droplets you exhale, which may contain viruses, from <a href="https://www.ucsf.edu/news/2020/06/417906/still-confused-about-masks-heres-science-behind-how-face-masks-prevent" target="_blank">spreading</a>. They have also been shown to reduce the number of droplets from other people's breath that reach your face, potentially preventing you from getting <a href="https://www.npr.org/sections/health-shots/2020/06/21/880832213/yes-wearing-masks-helps-heres-why" target="_blank" rel="noopener noreferrer">sick</a>. Given that face masks lack a large hole in them, as shields or masks with valves do, they allow far fewer droplets to escape than the competition. </p><p>The study considered the differences between a cheaply made face mask and a well-made one, with the cheap one proving much less effective. Even the best masks have some degree of leakage, so maintaining social distancing of at least two meters (about six feet) is still necessary. </p><p>No protective mask is perfect, and no set of rules offers complete safety. However, some objects and procedures work better than others at keeping people safe. As this study shows, face shields, masks with exhaustion valves, and cheaply made masks don't work as well as a well-made face mask.</p>
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Does warm weather impact COVID-19?
Various studies examine the impact of humidity, temperature, rain, and sunshine on COVID-19.
01 September, 2020
- Researchers around the world have been working to analyze and understand this virus since the global pandemic started earlier this year.
- While the first SARS-CoV virus (2003) did not circulate long enough for researchers to distinguish any specific seasonal pattern, daily weather did have an impact on the number of cases.
- Other studies from China, Australia, Brazil, and the UK take a look at how our weather can impact the transmission of COVID-19.
<p>Many people believe warmer weather protects us from respiratory illnesses - but the reality is that COVID-19 is unlike many of the other respiratory illnesses we've seen. Researchers around the world have been working to analyze and understand this virus since the global pandemic started earlier this year.</p><ul class="ee-ul"></ul>
How does weather impact virus transmission?
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU5OTg4OC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNTU1NjA2MX0.SvtcZz2PxVjC9AFLhC0sRpMDbcFp-RkAPJhuwTsZyWg/img.jpg?width=1245&coordinates=0%2C0%2C100%2C0&height=700" id="e5f2d" class="rm-shortcode" data-rm-shortcode-id="92f1bc5a03e54cc3f2f981acd09d14e2" data-rm-shortcode-name="rebelmouse-image" alt="COVID-19 virus SARS-CoV-2 under microscope weather virus" />How does weather impact the COVID-19 virus?
Image by MIA Studio on Shutterstock
<p><strong>Studies of the first SARS-CoV (in 2003) might help us understand.</strong><br></p><p>While this virus did not circulate long enough for researchers to distinguish any specific seasonal pattern, daily weather did have an impact on the number of cases. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870397/" target="_blank" rel="noopener noreferrer">According to this study</a>, new cases of SARS-CoV were 18x higher in lower temperatures (under 24.6°C). </p><p><strong>Cold weather impacts your likelihood of getting sick in different ways. </strong></p><p>One factor, according to <a href="https://sciencing.com/cold-weather-affect-immunity-22739.html" target="_blank" rel="noopener noreferrer">Sciencing</a>, that may increase your susceptibility in cold weather is how your sinuses respond to the humidity and temperature changes. Your nose is a natural air filter for your body. When you spend time in cold temperatures, your nasal passages dry out due to the constriction of blood vessels. When you return to warmer temperatures (like coming inside after time spent out in the cold), the sudden influx of moisture can cause your nose to run.</p><p>This usually forces you to breathe through your mouth, robbing you of the filter and making you susceptible to viruses or bacteria in the air. </p><p><strong>Cold weather = more time spent indoors, which can increase the likelihood of transmission.</strong></p><p>Regardless of the weather, it takes exposure to a virus to get a virus. One common reason why virus infections may become more common during cold months is that more people are spending time indoors (and together). </p><p><a href="https://bigthink.com/politics-current-affairs/social-distancing-math" target="_self">As research has determined</a>, social distancing can heavily impact the spread of the COVID-19 virus. Being clustered closer together indoors can increase the likelihood of transmission, giving the effect of the virus spreading faster in the colder months. </p>The weather and COVID-19 studies from around the globe
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU5OTg5MC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNTcwNzgxNH0.t5SY7q3HULHvoWIz5SpPA-DnPHjcgZqa0fANRn8ksxI/img.jpg?width=1245&coordinates=0%2C52%2C0%2C52&height=700" id="fb167" class="rm-shortcode" data-rm-shortcode-id="f3c84c531fb1b51decdb63e5f4a7c516" data-rm-shortcode-name="rebelmouse-image" alt="concept of condensation humidity impact COVID-19 condensation on window" />How do things like humidity, rainfall and sunshine impact the spread of COVID-19?
Photo by matuska on Shutterstock
<p>Laboratory and observational studies of COVID-19 patients have shown there is an impact of humidity on SARS-COV-2.</p><p><strong>Humidity and its impact on COVID-19:</strong></p><p><a href="https://wwwnc.cdc.gov/eid/article/26/9/20-1806_article#r7" target="_blank" rel="noopener noreferrer">A lab-generated aerosol of SARS-CoV-2</a> was stable at a humidity of 53 percent at room temperature (23°C). The virus had not degenerated much, even after 16 hours, and was more robust than SARS-CoV. </p><p>Although laboratory studies cannot be used to explicitly explain how the virus will act in the real world, these findings are very important in deepening our understanding of the virus and its transmission. </p><p><a href="https://www.sciencedirect.com/science/article/pii/S004896972032026X?via%3Dihub" target="_blank" rel="noopener noreferrer">Another study in China</a> (with more than 50 cases of COVID-19) found a link between humidity and reductions in COVID-19 cases. In this simulation, the team measured humidity as absolute humidity (the total amount of water in the air) and found that for every gram per cubic meter in absolute humidity, there was a 67 percent reduction in COVID-19 cases after a lag of 14 days. </p><p>Similar studies (with similar results) have been conducted in <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/tbed.13631" target="_blank" rel="noopener noreferrer">Australia</a>.</p><p><strong>Rainfall and its impact on COVID-19:</strong></p><p>Rainfall may also impact the spread of the virus. <a href="https://www.sciencedirect.com/science/article/pii/S0048969720325146?via%3Dihub" target="_blank" rel="noopener noreferrer">Research out of Brazil</a> looked at rainfall worldwide and confirmed a pattern: for each average inch per day of rain, there was an increase of 56 COVID-19 cases per day. There was no link found between the COVID-19 deaths and rainfall. </p><p><strong>Sunshine and its impact on COVID-19: </strong></p><p>A Spain study found (after 5 days of lockdown) the longer the hours of sunshine, the more cases there were of the virus. This positive association held true with a lag (between sunshine hours and cases) of both 8 and 11 days. </p><p>However, it's important to note that this actually contradicts findings from Influenza research, which suggests a lower transmission with longer hours of sunshine. While influenza and COVID-19 are obviously different, it's interesting to note this contrast, as they are both viral infections.</p><p><strong>While all of these studies are interesting, does it really prove COVID-19 is impacted by weather? </strong></p><p><a href="https://www.medrxiv.org/content/10.1101/2020.05.21.20108803v1" target="_blank" rel="noopener noreferrer">Research out of Oxford</a> actually lists reasons why people should not use these observational studies on the weather and COVID-19 cases to establish if the virus is more or less transmittable based on the season. </p><p>While it's important to note that there are still things we don't know about COVID-19 and that each country has different testing and studying methods, the more we know about how this virus behaves in different climates the more we can work to prevent further infection. </p>
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First case of COVID-19 reinfection reported in Hong Kong
The patient's second infection was asymptomatic, suggesting that subsequent infections may be milder.
24 August, 2020
(Photo by Antonio Masiello/Getty Images)
- A 33-year-old man contracted the virus first in March, then again in August.
- Researchers at the University of Hong Kong compared the RNA of the two infections, finding them to be distinct.
- The immune system's response to the coronavirus remains unclear, but recent studies suggest T cells may help to battle subsequent infections even after antibody levels drop.
<p>A man in Hong Kong was infected with SARS-CoV-2 for a second time, becoming the first confirmed case of reinfection, according to researchers at the University of Hong Kong.</p><p>The patient is a <a href="https://www.statnews.com/2020/08/24/first-covid-19-reinfection-documented-in-hong-kong-researchers-say/" target="_blank">33-year-old man who first contracted the virus in March</a>, and then again more than four months later while traveling in Europe. Since the coronavirus was first reported, scientists have been trying to figure out whether it's possible to contract the virus multiple times, as is possible with other coronaviruses.</p><p>But despite some anecdotal reports of reinfection, the Hong Kong patient is the first confirmed case. To make sure the second infection was unrelated to the first, the researchers sequenced the virus from both infections and compared the RNA. They found a significant difference between the samples.</p>
<p style="margin-left: 20px;">"This is the world's first documentation of a patient who recovered from Covid-19 but got another episode of Covid-19 afterwards," the researchers said in a statement.</p><p><span></span>On one level, it may be discouraging to learn that it's possible to contract SARS-CoV-2 twice. But the researchers noted that the Hong Kong case might be an outlier, and that reinfection could be rare throughout the population. What's more, the paper described the patient's first case as mild and his second case as asymptomatic.<br></p><p>That's promising news, because it suggests that while the patient's immunity wasn't strong enough to prevent infection, it was strong enough to protect him from developing COVID-19, the disease caused by the virus.</p>
<div id="741d8" class="rm-shortcode" data-rm-shortcode-id="816166c00fb12a3743c23ed30e8a391f"><blockquote class="twitter-tweet twitter-custom-tweet" data-twitter-tweet-id="1297890426024800272" data-partner="rebelmouse"><div style="margin:1em 0">1) Second infection was asymptomatic. While immunity was not enough to block reinfection, it protected the person f… https://t.co/887j4nAXNJ</div> — Prof. Akiko Iwasaki (@Prof. Akiko Iwasaki)<a href="https://twitter.com/VirusesImmunity/statuses/1297890426024800272">1598276165.0</a></blockquote></div><p>Still, the processes behind the immune response to the virus remain unclear. Earlier in August, the Centers for Disease Control and Prevention issued <a href="https://www.cdc.gov/media/releases/2020/s0814-updated-isolation-guidance.html" target="_blank" rel="noopener noreferrer dofollow">new guidelines</a> saying that immunity from COVID-19 likely only lasts three months after contraction, while studies have suggested that antibodies seem to fade away after a few months.</p><p>But antibodies aren't the whole story. The immune system also has T cells and B cells — the so-called "memory" cells that are able to remember a virus, and then strategically mobilize the immune system against it if it enters the body again. That may help to explain why the Hong Kong patient's second infection was asymptomatic.</p>
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU3NzQzOS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNTg0ODAzNH0.I9albN7u2TCuTYsVaNobi9HFlQf-2lj_2MEjj-vFclE/img.jpg?width=980" id="92a98" class="rm-shortcode" data-rm-shortcode-id="08fb94da74e5180559c81160e8b72a66" data-rm-shortcode-name="rebelmouse-image" alt="Coronavirus research" />Researchers Work On Developing Test For Coronavirus At Hackensack Meridian's Center For Discovery and Innovation
<p class=""><br></p>(Photo by Kena Betancur/Getty Images)
<p>It'll take time to know how common reinfection is, how durable the immune response is, and how the <a href="https://www.healthline.com/health-news/what-to-know-about-mutation-and-covid-19" target="_blank">inevitable mutation</a> of the virus impacts efforts to develop a vaccine.</p><p style="margin-left: 20px;">"It may be completely different with this coronavirus," Dr. Anthony Fauci, who heads the National Institute of Allergy and Infectious Diseases, said in an <a href="https://jamanetwork.com/journals/jama/fullarticle/2767208" target="_blank">interview with the medical journal JAMA</a>. "It may be that people induce a response that's quite durable. But if it acts like common coronaviruses, it likely is not going to be a very long duration of immunity."</p>
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Engineers use “DNA origami” to identify vaccine design rules
DNA molecules are highly programmable.
23 August, 2020
Matt Cardy/Getty Images
By folding DNA into a virus-like structure, MIT researchers have designed HIV-like particles that provoke a strong immune response from human immune cells grown in a lab dish. Such particles might eventually be used as an HIV vaccine.
<p>The DNA particles, which closely mimic the size and shape of viruses, are coated with HIV proteins, or antigens, arranged in precise patterns designed to provoke a strong immune response. The researchers are now working on adapting this approach to develop a potential vaccine for SARS-CoV-2, and they anticipate it could work for a wide variety of viral diseases.</p><p>"The rough design rules that are starting to come out of this work should be generically applicable across disease antigens and diseases," says Darrell Irvine, who is the Underwood-Prescott Professor with appointments in the departments of Biological Engineering and Materials Science and Engineering; an associate director of MIT's Koch Institute for Integrative Cancer Research; and a member of the Ragon Institute of MGH, MIT, and Harvard.</p><p>Irvine and Mark Bathe, an MIT professor of biological engineering and an associate member of the Broad Institute of MIT and Harvard, are the senior authors of the study, which appears today in <em>Nature Nanotechnology</em>. The paper's lead authors are former MIT postdocs Rémi Veneziano and Tyson Moyer.</p>
<h3>DNA design</h3><p>Because DNA molecules are highly programmable, scientists have been working since the 1980s on methods to design DNA molecules that could be used for drug delivery and many other applications, most recently using a technique called DNA origami that was invented in 2006 by Paul Rothemund of Caltech.</p><p>In 2016, Bathe's lab developed an algorithm that can automatically design and build arbitrary three-dimensional <a href="http://news.mit.edu/2016/automating-dna-origami-opens-door-many-new-uses-0526" target="_blank" rel="noopener noreferrer dofollow">virus-like shapes</a> using DNA origami. This method offers precise control over the structure of synthetic DNA, allowing researchers to attach a variety of molecules, such as viral antigens, at specific locations.</p><p>"The DNA structure is like a pegboard where the antigens can be attached at any position," Bathe says. "These virus-like particles have now enabled us to reveal fundamental molecular principles of immune cell recognition for the first time."</p><p>Natural viruses are nanoparticles with antigens arrayed on the particle surface, and it is thought that the immune system (especially B cells) has evolved to efficiently recognize such particulate antigens. Vaccines are now being developed to mimic natural viral structures, and such nanoparticle vaccines are believed to be very effective at producing a B cell immune response because they are the right size to be carried to the lymphatic vessels, which send them directly to B cells waiting in the lymph nodes. The particles are also the right size to interact with B cells and can present a dense array of viral particles.</p>
<p>However, determining the right particle size, spacing between antigens, and number of antigens per particle to optimally stimulate B cells (which bind to target antigens through their B cell receptors) has been a challenge. Bathe and Irvine set out to use these DNA scaffolds to mimic such viral and vaccine particle structures, in hopes of discovering the best particle designs for B cell activation.</p><p>"There is a lot of interest in the use of virus-like particle structures, where you take a vaccine antigen and array it on the surface of a particle, to drive optimal B-cell responses," Irvine says. "However, the rules for how to design that display are really not well-understood."</p><p>Other researchers have tried to create subunit vaccines using other kinds of synthetic particles, such as polymers, liposomes, or self-assembling proteins, but with those materials, it is not possible to control the placement of viral proteins as precisely as with DNA origami.</p>
<p>For this study, the researchers designed icosahedral particles with a similar size and shape as a typical virus. They attached an engineered HIV antigen related to the gp120 protein to the scaffold at a variety of distances and densities. To their surprise, they found that the vaccines that produced the strongest response B cell responses were not necessarily those that packed the antigens as closely as possible on the scaffold surface.</p><p>"It is often assumed that the higher the antigen density, the better, with the idea that bringing B cell receptors as close together as possible is what drives signaling. However, the experimental result, which was very clear, was that actually the closest possible spacing we could make was not the best. And, and as you widen the distance between two antigens, signaling increased," Irvine says.</p><p>The findings from this study have the potential to guide HIV vaccine development, as the HIV antigen used in these studies is currently being tested in a clinical trial in humans, using a protein nanoparticle scaffold.</p><p>Based on their data, the MIT researchers worked with Jayajit Das, a professor of immunology and microbiology at Ohio State University, to develop a model to explain why greater distances between antigens produce better results. When antigens bind to receptors on the surface of B cells, the activated receptors crosslink with each other inside the cell, enhancing their response. However, the model suggests that if the antigens are too close together, this response is diminished.</p>
<h3>Beyond HIV</h3><p>In recent months, Bathe's lab has created a variant of this vaccine with the Aaron Schmidt and Daniel Lingwood labs at the Ragon Institute, in which they swapped out the HIV antigens for a protein found on the surface of the SARS-CoV-2 virus. They are now testing whether this vaccine will produce an effective response against the coronavirus SARS-CoV-2 in isolated B cells, and in mice.</p><p>"Our platform technology allows you to easily swap out different subunit antigens and peptides from different types of viruses to test whether they may potentially be functional as vaccines," Bathe says.</p><p>Because this approach allows for antigens from different viruses to be carried on the same DNA scaffold, it could be possible to design variants that target multiple types of coronaviruses, including past and potentially future variants that may emerge, the researchers say.</p><p>Bathe was recently awarded a grant from the Fast Grants Covid-19 fund to develop their SARS-CoV-2 vaccine. The HIV research presented in the <em>Nature Nanotechnology</em> paper was funded by the Human Frontier Science Program, the U.S. Office of Naval Research, the U.S. Army Research Office through MIT's Institute for Soldier Nanotechnologies, the Ragon Institute, and the U.S. National Institutes of Health.</p><p>Reprinted with permission of <a href="http://news.mit.edu/" target="_blank" rel="noopener noreferrer dofollow">MIT News</a>. Read the <a href="https://news.mit.edu/2020/dna-origami-vaccine-design-rules-0629" target="_blank">original article</a>.</p>
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