{"id":5753,"date":"2014-04-29T10:00:44","date_gmt":"2014-04-29T14:00:44","guid":{"rendered":"https:\/\/blogs.nature.com\/spoonful\/?p=5753"},"modified":"2014-05-15T11:26:12","modified_gmt":"2014-05-15T15:26:12","slug":"ebola-outbreak-in-west-africa-lends-urgency-to-recently-funded-research","status":"publish","type":"post","link":"https:\/\/blogs.nature.com\/spoonful\/2014\/04\/ebola-outbreak-in-west-africa-lends-urgency-to-recently-funded-research.html","title":{"rendered":"Ebola outbreak in West Africa lends urgency to recently-funded research"},"content":{"rendered":"
\"Electron<\/a>

Electron micrograph of Ebola virus{credit}CDC\/ Frederick Murphy{\/credit}<\/p><\/div>\n

Earlier this year, the Ebola virus popped up for the first time ever in West Africa. How it got there, some 2,000 miles from previous Ebola hotspots in remote parts of Central Africa, remains a mystery. Experts are particularly concerned about the current outbreak<\/a>, which has sickened more than 250 and killed at least 140, because the pathogen has made its way into Conakry, the densely populated capital city of Guinea.<\/p>\n

Unfortunately, there are no vaccines or treatments approved to work specifically against the virus, which first emerged in the forests of Zaire (now the Democratic Republic of Congo) in 1976. The virus\u2019s high virulence and lethality make it challenging to study, and its rarity means that any effective therapeutics that are developed will likely have limited commercial potential, leaving pharmaceutical companies little financial incentive to develop treatments against the pathogen.<\/p>\n

Very few candidate therapeutics against Ebola\u00a0have proven effective in non-human primates, the gold-standard animal model for research against such viruses. But there is, amidst the ongoing outbreak, mobilization of funding toward anti-Ebola agents that have proven their mettle in such models: last month the US National Institutes of Health announced that it was putting a combined total of more than $50 million towards a handful of the most promising approaches.<\/p>\n

<\/p>\n

About half of that money<\/a> will support a five-year collaborative research effort spanning 20 labs in seven countries to develop a cocktail of antibodies that neutralize the virus. Various research groups have already identified 150 or so neutralizing antibodies against the Zaire strain of the virus, a variant<\/a> of which is responsible for the current outbreak, says Erica Saphire<\/a>, a virologist at The Scripps Research Institute in La Jolla who is leading the consortium. The members of the collaboration are \u201cputting all of their antibodies in and we\u2019re going to compare them side-by-side and figure out which ones are best and why,\u201d she says.<\/p>\n

Researchers already know that mixtures of neutralizing antibodies can thwart the virus in non-human primates. For example, consortium member Gary Kobinger<\/a> and his colleagues at the Public Health Agency of Canada in Winnepeg reported<\/a> in June 2012 that a mixture of three anti-Ebola virus antibodies saved the lives of cynomolgus macaques when administered up to two days after a lethal dose of the virus.<\/p>\n

A few months after Kobinger\u2019s study was published, researchers from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) in Frederick, Maryland and San Diego-based Mapp Biopharmaceutical<\/a> obtained similar results<\/a> using a different antibody cocktail in rhesus macaques. \u201cRather than compete against each other, we figured we\u2019d work together to figure out which antibodies from each cocktail are the best,\u201d says Larry Zeitlin, president of Mapp and co-author of the rhesus macaque study who is also a member of the new consortium. Zeitlin says the group\u2019s latest cocktail contains a mixture of two antibodies developed by the Canadian team and one from the US bunch. \u201cWe expect to be doing a phase 1 safety trial in the first half of 2015,\u201d Zeitlin says.<\/p>\n

A bevy of options<\/b><\/p>\n

The other half<\/a> of the new funding the NIH announced last month is going toward a multi-center collaboration led by Ebola researcher Thomas Geisbert<\/a> at the University of Texas Medical Branch in Galveston. The five-year effort brings together academic researchers and scientists from Profectus BioSciences<\/a> in Baltimore, Maryland, and Canada\u2019s Tekmira Pharmaceuticals<\/a>. The partnership aims to advance several different types of therapeutics for Ebola virus and the related Marburg virus, which also causes hemorrhagic fevers in humans.<\/p>\n

One of the group\u2019s candidate therapeutics is a vaccine<\/a> containing a form of the vesicular stomatitis virus (VSV) engineered to contain a gene from the Zaire strain of the Ebola virus (they\u2019ve also devised similar vaccines for Marburg virus as well as a different strain of Ebola virus). Geisbert\u2019s lab has shown that a single shot of the vaccine saves rhesus macaques<\/a> from a lethal dose of Ebola virus.<\/p>\n

For their part, Profectus is investigating the prophylactic effectiveness of the vaccine, and is applying for funds to test the VSV-based Ebola vaccine in humans, according to John Eldridge, the company\u2019s chief scientist. Profectus has already tested VSV-based vaccines against HIV in humans, Eldridge says, \u201cso we know the vaccine vector is safe and immunogenic.\u201d Still, Geisbert points out that \u201cfor any of these vaccines, we\u2019re talking years from being ready to use in humans.\u201d<\/p>\n

However, another therapy Geisbert\u2019s group is investigating may be ready sooner. It\u2019s an RNA interference (RNAi)-based drug that silences certain genes in the Zaire strain of Ebola virus. The treatment, developed by Tekmira and known as TKM-Ebola, protected rhesus monkeys<\/a> from a lethal dose of the virus. Backed by $140 million from the US Department of Defense, the company began phase 1 tests<\/a> of TKM-Ebola in healthy human volunteers in January. And in early March<\/a>, the FDA gave the drug fast-track status to expedite its development.<\/p>\n

Geisbert\u2019s team will also investigate combination therapies, such as Profectus\u2019s vaccine given in combination with Tekmira\u2019s RNAi drug. \u201cCombinations may work more effectively or more efficiently than any approach alone,\u201d Eldridge says. \u201cI don\u2019t think anyone\u2019s presumptuous enough to think they have the answer all by themselves.\u201d<\/p>\n

All treatments, big and small<\/b><\/p>\n

Most of the proposed Ebola treatments target a single strain of the virus. But one team of researchers at the USAMRIID and North Carolina-based BioCryst Pharmaceuticals<\/a> has been working on a small molecule with broad antiviral activity. The compound, BCX4430, blocks the replication of RNA viruses like Ebola and Marburg. The team showed last month that the drug protected<\/a> cynomolgus macaques against Marburg virus and shielded rodents from Marburg and Ebola virus infections. \u201cWe are looking forward to starting a phase 1 clinical trial early next year,\u201d says Sina Bavari, a microbiologist at USAMRIID who is leading the work.<\/p>\n

Under the US Food and Drug Administration\u2019s so-called \u2018animal rule<\/a>,\u2019 these experimental treatments for Ebola\u2014for which it would be impractical or unethical to demonstrate efficacy in humans\u2014can be licensed for human use provided that phase 1 trials demonstrate that they are safe in humans. However, aside from Tekmira\u2019s RNAi therapy for Ebola, the phase 1 trial of which is slated to wrap up by the middle of this year, none of these treatments appears likely to clear human safety tests any time soon. \u201cIt\u2019s always difficult to see an ongoing outbreak, and we haven\u2019t had time to cross all those tests for licensure,\u201d Kobinger says. But, he adds, \u201cwe\u2019re really hoping that we\u2019ll have something in place for the next outbreak.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

Earlier this year, the Ebola virus popped up for the first time ever in West Africa. How it got there, some 2,000 miles from previous Ebola hotspots in remote parts of Central Africa, remains a mystery. Experts are particularly concerned about the current outbreak, which has sickened more than 250 and killed at least 140, because the pathogen has made its way into Conakry, the densely populated capital city of Guinea.  Read more<\/a> Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":44569,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[136,135],"tags":[337,257,256],"class_list":["post-5753","post","type-post","status-publish","format-standard","hentry","category-infectious-diseases","category-virology","tag-ebola","tag-infection","tag-virology-2"],"_links":{"self":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts\/5753","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/users\/44569"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/comments?post=5753"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts\/5753\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/media?parent=5753"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/categories?post=5753"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/tags?post=5753"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}