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Experimental vaccine protects against diverse Ebola strains

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The ebola virus is very deadly, and we still are unsure of how it infects humans. (Image: CDC)

It was not long ago that I had posted a two-part story about Ebola virus here on AAAS MemberCentral: "Ebola virus: A brief look into the past" and "Ebola virus: Current developments". The recent outbreak of Ebola virus in Uganda has prompted attention to the topic yet again. A number of individuals have already died, and authorities are currently trying to contain the spread of the virus.

In light of these events, I decided to revisit the topic and ask one of our AAAS fellows, Gary Nabel of the National Institute of Allergy and Infectious Diseases (NIAID) and director of NIAID's Vaccine Research Center, a few questions about Ebola and the potential for vaccine development. Nabel is known  "for distinguished contributions to virology and immunology in his own research and for his leadership efforts to develop vaccines against HIV, Ebola and other viruses."

How close are we to developing a vaccine for Ebola virus? Would such a vaccine be able to protect against all currently known strains?
AAAS Fellow, Gary Nabel director of the NIAID Vaccine Research Center: The VRC is advancing an experimental Ebola vaccine into clinical trials that protects against diverse Ebola strains in monkey models, including the Sudan/Gulu, Zaire, and Bundiboyo species.

What are some of the main difficulties that have prevented the successful development of a vaccine thus far?
Nabel: Protection against Ebola virus depends on strong cellular immune responses that mobilize CD8 cells to kill virus-infected cells. Our first generation vaccine, an Ad5 vectored GP, was quite effective in monkeys, but humans have a high degree of seropositivity to Ad5, which counteracts its protective effect. We therefore had to develop a new vector.

A recent research paper identified the protein NPC-1 as a site that the Ebola virus uses to enter human cells. The paper also discusses the potential of drugs that could block the site to prevent infection of a cell by the virus. One of the compounds found to block this protein was imipramine, an antidepressant. Could such drugs be used for prevention, and are any drugs currently used for chemoprophylaxis against Ebola virus?
Nabel: There are now several drugs that appear to inhibit Ebola virus replication in the lab through different mechanisms. For example, we have found that some licensed c-ABL tyrosine kinase inhibitors also exert antiviral effects. But it would not be appropriate to use such drugs in an outbreak setting until/unless they have shown protective efficacy in monkeys.

Why is it that Ebola virus appears to be eradicated and then springs up a few years later somewhere else? Is there a natural reservoir for Ebola virus?
Nabel: There is likely to be an animal reservoir for Ebola virus but the exact carrier species is controversial. Some have suggested bats and others have suggested dingos or apes. This point has not been definitively addressed.

So far, the virus has remained isolated within central Africa — do you feel that this is likely to change in the future?
Nabel: It remains possible that the virus could spread to other regions of the world, carried either by infected animals or humans. The related Marburg virus outbreak was originally detected in humans in Germany. There have been Ebola outbreaks in animals in Reston, Virginia, and in pigs in the Philippines. While it did not spread to humans in those cases, it suggests that such spread could occur.