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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<div about="/news-events/nih-research-matters/llama-antibody-engineered-block-coronavirus" typeof="sioc:Item foaf:Document" class="ds-1col node node--nih-research-matters view-mode-full node--full node--nih-research-matters--full clearfix">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2020-05-19T00:00:00-04:00" class="date-display-single">May 19, 2020</span></p><div class='syndicate'><h1>Llama antibody engineered to block coronavirus</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>Based on antibodies isolated from llamas, researchers engineered an antibody that prevented SARS-CoV-2, the virus that causes COVID-19, from entering cells in laboratory experiments.</li>
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<li>Follow-up work is being planned to test the antibody in animal models of the disease.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Llamas on farm">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2020/20200519-llama.jpg?itok=GTcDPQd9&timestamp=1589834734 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2020/20200519-llama.jpg?itok=VH0LD2fr&timestamp=1589834734 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2020/20200519-llama.jpg?itok=Y1J7O336&timestamp=1589834734 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2020/20200519-llama.jpg?itok=eQZITfC8&timestamp=1589834734 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2020/20200519-llama.jpg?itok=_0Nta6Uq&timestamp=1589834734 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2020/20200519-llama.jpg?itok=VH0LD2fr&timestamp=1589834734" alt="Llamas on farm" title="Llamas on farm" />
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||
</picture><span class="caption">Llamas and other animals make small antibodies that might serve as the basis for potential therapeutics. This llama, which made the antibodies used in this study, is four years old and still living on a farm in the Belgian countryside operated by Ghent University’s Vlaams Institute for Biotechnology. </span><span class="credit">Tim Coppens</span></div>
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</div><p>Animals produce antibodies much like those made by the human immune system. But some animals, such as llamas, also produce another type of antibody that’s only about a quarter of the size of a typical human antibody. Such “single-domain” antibodies, or nanobodies, have several features that make them of interest as potential therapeutics.</p>
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<p>Nanobodies are very stable, so they could potentially be stored for a long time after production. They can also be delivered by an inhaler directly to the lungs, which makes them particularly promising for respiratory infections such as COVID-19.</p>
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<p>The World Health Organization declared COVID-19 an international pandemic on March 11, 2020. To date, it has infected more than 4 million people worldwide and killed over a quarter million. Researchers are rushing to develop vaccines. In the meantime, effective treatments are urgently needed.</p>
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<p>Researchers led by Daniel Wrapp and Dr. Jason McLellan from the University of Texas, in collaboration with a Belgian research team, had developed nanobodies from llamas for research into Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Both these diseases are caused by coronaviruses related to SARS-CoV-2.</p>
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<div class="media-float-right"><div class="media media-element-container media-floated_media"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2020/20200515-camelid-antibody.jpg?itok=MwEs6Ywn&timestamp=1589895881 1x" media="screen and (min-width: 960px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2020/20200515-camelid-antibody.jpg?itok=4j5Wa_5v&timestamp=1589895881 1x" media="screen and (min-width: 800px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2020/20200515-camelid-antibody.jpg?itok=octpaK6S&timestamp=1589895881 1x" media="screen and (min-width: 600px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2020/20200515-camelid-antibody.jpg?itok=q_uNQo7G&timestamp=1589895881 1x" media="screen and (min-width: 480px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2020/20200515-camelid-antibody.jpg?itok=jhrJ6pmD&timestamp=1589895881 1x" media="screen and (min-width: 0)"></source>
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<!--[if IE 9]></video><![endif]-->
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<img class="media-element" src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2020/20200515-camelid-antibody.jpg?itok=4j5Wa_5v&timestamp=1589895881" alt="Antibody bound to SARS-CoV-2" title="Antibody bound to SARS-CoV-2" />
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</picture><span class="caption">An antibody called VHH-72Fc (blue) binds tightly to the spike protein on SARS-CoV-2 (pink, green and orange), blocking the virus from infecting cells in culture. </span><span class="credit">University of Texas at Austin</span></div>
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</div></div>
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<p>The team injected a llama with forms of the viruses’ spike proteins. Spike proteins are found on the surface of coronaviruses. They latch onto cells, then undergo a structural change that allows the virus to fuse with the cell. Once the virus enters the host cell, it can copy itself and produce more viruses. The nanobodies that the scientists harvested from the llama bloodstream and produced in the lab bound to the spike protein and prevented the virus from entering cells. </p>
|
||
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||
<p>The researchers decided to test whether any of the nanobodies they had developed could also stop SARS-CoV-2 from infecting cells. Their work was funded in part by NIH’s National Institute of Allergy and Infectious Disease (NIAID). Results were published on May 5, 2020, in <em>Cell</em>.</p>
|
||
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||
<p>Out of the 12 nanobodies targeting either the SARS or MERS viruses, one called SARS VHH-72 showed an ability to bind to the spike protein on SARS-CoV-2 as well. However, it also unbound quickly, which made it unlikely to prevent the virus from entering cells.</p>
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<p>The researchers analyzed the structure of the antibody bound to the spike proteins of the SARS and MERS viruses. Based on this analysis and <a href="https://www.nih.gov/news-events/nih-research-matters/novel-coronavirus-structure-reveals-targets-vaccines-treatments">previous work</a> revealing the structure of the SARS-CoV-2 spike protein, they were able to engineer the nanobody to stick more tenaciously to the virus. They did this by fusing two copies of the nanobody together.</p>
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||
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||
<p>The engineered nanobody bound strongly to SARS-CoV-2 and was able to stop the virus from entering cells in laboratory experiments.</p>
|
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<p>“This is one of the first antibodies known to neutralize SARS-CoV-2,” McLellan says.</p>
|
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<p>The researchers are planning follow-up experiments in animals, with the hopes of eventually testing their nanobody in human trials. Antibody therapy could potentially be used as a treatment for people who are already infected or at high risk of becoming infected.</p>
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<p>—by Sharon Reynolds</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/microneedle-coronavirus-vaccine-triggers-immune-response-mice" target="_top">Microneedle Coronavirus Vaccine Triggers Immune Response in Mice</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/study-suggests-new-coronavirus-may-remain-surfaces-days" target="_top">Study Suggests New Coronavirus May Remain on Surfaces for Days</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/novel-coronavirus-structure-reveals-targets-vaccines-treatments" target="_top">Novel Coronavirus Structure Reveals Targets for Vaccines and Treatments</a></li><li><a href="https://directorsblog.nih.gov/2018/11/13/looking-to-llamas-for-new-ways-to-fight-the-flu/" target="_top">Looking to Llamas for New Ways to Fight the Flu</a></li><li><a href="https://www.nih.gov/health-information/coronavirus" target="_top">Coronavirus (COVID-19)</a></li><li><a href="https://www.niaid.nih.gov/diseases-conditions/coronaviruses" target="_top">Coronaviruses</a></li><li><a href="https://www.coronavirus.gov/" target="_top">Coronavirus (COVID-19) (CDC)</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://www.ncbi.nlm.nih.gov/pubmed/32375025">Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.</a> Wrapp D, De Vlieger D, Corbett KS, Torres GM, Wang N, Van Breedam W, Roose K, van Schie L; VIB-CMB COVID-19 Response Team, Hoffmann M, Pöhlmann S, Graham BS, Callewaert N, Schepens B, Saelens X, McLellan JS. Cell. 2020 Apr 29. pii: S0092-8674(20)30494-3. doi: 10.1016/j.cell.2020.04.031. [Epub ahead of print] PMID: 32375025.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Allergy and Infectious Disease (NIAID); Vlaams Instituut voor Biotechnologie; Ghent University; Research Foundation – Flanders; Agentschap Innoveren & Ondernemen; RAPID Consortium.</p>
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