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Genome Medicine | Full text | Tackling Ebola: new insights into prophylactic and therapeutic intervention strategies

Genome Medicine | Full text | Tackling Ebola: new insights into prophylactic and therapeutic intervention strategies



Tackling Ebola: new insights into prophylactic and therapeutic intervention strategies

Emmie de WitHeinz Feldmann and Vincent J Munster*
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, 903 South 4th Street, MT 59840, USA
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Genome Medicine 2011, 3:5  doi:10.1186/gm219

The electronic version of this article is the complete one and can be found online at:http://genomemedicine.com/content/3/1/5

Published:27 January 2011
© 2011 BioMed Central Ltd 

Abstract

Since its discovery in 1976, Ebolavirus has caused periodic outbreaks of viral hemorrhagic fever associated with severe and often fatal disease. Ebolavirus is endemic in Central Africa and the Philippines. Although there is currently no approved treatment available, the past 10 years has seen remarkable progress in our understanding of the pathogenicity of Ebolavirus and the development of prophylactic and post-exposure therapies against it. In vitro and in vivoexperiments have shown that Ebolavirus pathogenicity is multifactorial, including viral and host determinants. Besides their function in the virus replication cycle, the viral glycoprotein, nucleoprotein, minor matrix protein and polymerase cofactor are viral determinants of pathogenicity, with evasion of the host innate and adaptive immune responses as the main mechanism. Although no licensed Ebolavirus vaccines are currently available, vaccine research in non-human primates, the 'gold standard' animal model for Ebolavirus, has produced several promising candidates. A combination of DNA vaccination and a recombinant adenovirus serotype 5 boost resulted in cross-protective immunity in non-human primates. A recombinant vesicular stomatitis vaccine vector protected non-human primates in pre- and post-exposure challenge studies. Several antiviral therapies are currently under investigation, but only a few of these have been tested in non-human primate models. Antisense therapies, in which oligonucleotides inhibit viral replication, have shown promising results in non-human primates following post-exposure treatment. In light of the severity of Ebolavirus disease and the observed increase in Ebolavirus outbreaks over the past decade, the expedited translation of potential candidate therapeutics and vaccines from bench to bedside is currently the most challenging task for the field. Here, we review the current state of Ebolavirus research, with emphasis on prophylactic and therapeutic intervention strategies.

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