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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2016-03-08T00:00:00-05:00" class="date-display-single">March 8, 2016</span></p><div class='syndicate'><h1>Experimental Ebola antibody protects monkeys</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
<ul>
<li>A monoclonal antibody derived from a person who survived Ebola virus disease protected non-human primates when given as late as 5 days after Ebola infection.</li>
<li>The antibody can now advance to testing in humans as a potential treatment for Ebola virus disease.</li>
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2016/20160308-ebola.jpg?itok=nYdS8bqT&amp;timestamp=1457365993" alt="Ebola virus bound by antibodies" title="Ebola virus bound by antibodies" />
</picture><span class="caption">The Ebola virus surface glycoprotein (blue) is shown bound by protective antibodies mAb114 (pink/white) and mAb100 (purple/white). </span><span class="credit">NIAID</span></div>
</div><p>The Ebola virus causes acute disease that can lead to severe illness and death. It typically affects multiple organs in the body. Symptoms usually appear 2 to 21 days after exposure. Infection can cause fever, headache, body aches, weakness, stomach pain, and lack of appetite. Later symptoms include vomiting, diarrhea, and internal and external hemorrhage (bleeding).</p>
<p>There are currently no licensed treatments for Ebola virus infection. The 2014-2015 outbreak in West Africa, which caused more than 11,000 deaths, highlighted the need for effective therapies.</p>
<p>One experimental drug cocktail called ZMapp is now being evaluated in human trials. Developed by Mapp Biopharmaceutical Inc., ZMapp is composed of 3 different monoclonal antibodies (mAbs). These are made by immunizing mice and “cloning” the cells that produce the most effective antibodies.</p>
<p>A team of scientists led by Dr. Nancy J. Sullivan of NIHs National Institute of Allergy and Infectious Diseases (NIAID) set out to develop a simplified treatment with fewer antibodies by generating mAbs from human survivors of Ebola virus disease. Results appeared online in 2 papers on February 25, 2016, in <em>Science</em>.</p>
<p>The researchers obtained blood samples from a survivor of the 1995 Ebola outbreak in Kikwit, Democratic Republic of the Congo. Tests showed that, more than a decade after infection, the survivor retained antibodies against Ebola. Collaborators from the Institute for Research in Biomedicine in Switzerland then cloned antibody-producing B cells from the survivor to make mAbs for potential use as a therapeutic for Ebola infection.</p>
<p>The NIAID researchers found that 2 of the mAbs (mAb110 and mAb114) had unique properties and were the most potent against Ebola virus.</p>
<p>Collaborators from the U.S. Army Medical Research Institute of Infectious Diseases administered a lethal dose of <em>Zaire ebolavirus</em> to 4 rhesus macaques, then treated 3 of the animals, beginning a day later, with a mixture of the mAbs for 3 consecutive days. The untreated control macaque developed Ebola virus disease and succumbed to the virus, but the treated animals survived and remained free of Ebola symptoms.</p>
<p>Since mAb114 was the most potent mAb, the researchers tested it alone. They found that even when treatment began 5 days after virus exposure—a delay common in an outbreak setting—the treated animals survived and remained free of Ebola symptoms.</p>
<p>The NIAID team and Dartmouth College colleagues also performed a structural analysis, described in the second paper, of how mAb110 and mAb114 prevent the Ebola virus from entering target cells. Most notably, they found that mAb114 binds to a novel site of vulnerability on the Ebola virus that was previously thought to be unreachable by antibodies.</p>
<p>“The antibody mAb114 is the first to demonstrate the ability to neutralize the virus by this mechanism,” Sullivan says. “Together the evidence shows a single antibody could prove to be an effective therapy against Ebola virus disease and warrants further exploration in clinical trials.”</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/lipid-nanoparticle-therapeutic-treats-ebola-monkeys" target="_top">Lipid Nanoparticle Therapeutic Treats Ebola in Monkeys</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/ebola-vaccine-prompts-immune-response" target="_top">Ebola Vaccine Prompts Immune Response</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/computer-models-can-help-guide-ebola-response" target="_top">Computer Models Can Help Guide Ebola Response</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/genetics-2014-ebola-outbreak" target="_top">Genetics of the 2014 Ebola Outbreak</a></li><li><a href="http://www.niaid.nih.gov/topics/ebolamarburg" target="_top">Ebola and Marburg</a></li></ul><p class="footnote"><strong class="label-inline">References:&nbsp;</strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/26917593">Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody.</a> Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M, Wollen S, Ploquin A, Doria-Rose NA, Staupe RP, Bailey M, Shi W, Choe M, Marcus H, Thompson EA, Cagigi A, Silacci C, Fernandez-Rodriguez B, Perez L, Sallusto F, Vanzetta F, Agatic G, Cameroni E, Kisalu N, Gordon I, Ledgerwood JE, Mascola JR, Graham BS, Muyembe-Tamfun JJ, Trefry JC, Lanzavecchia A, Sullivan NJ. <em>Science</em>. 2016 Feb 25. pii: aad5224. [Epub ahead of print]. PMID: 26917593.<br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/26917592">Structural and molecular basis for Ebola virus neutralization by protective human antibodies.</a> Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS. <em>Science</em>. 2016 Feb 25. pii: aad6117. [Epub ahead of print]. PMID: 26917592.</p><p class="footnote"><strong class="label-inline">Funding:&nbsp;</strong>NIHs National Institute of Allergy and Infectious Diseases (NIAID).</p>
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