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 vivo experiments 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.
Highlights
Introduction e genusEbolavirus (EBOV) in the Filoviridae family contains five distinct species [1]
Ebolaviruses are known for their ability to cause devastating viral hemorrhagic fever outbreaks in humans and great apes, but the natural reservoir for EBOV has remained elusive for many years
One of these occurred in the Democratic Republic of Congo and was caused by Zaire ebolavirus (ZEBOV) [6], whereas the other, unrelated outbreak that occurred in Sudan was caused by Sudan
Summary
USDA issues license for West Nile DNA vaccine for horses [http://www.aphis.usda.gov/lpa/news/2005/07/wnvdna_vs.html]. Jones SM, Feldmann H, Stroher U, Geisbert JB, Fernando L, Grolla A, Klenk HD, Sullivan NJ, Volchkov VE, Fritz EA, Daddario KM, Hensley LE, Jahrling PB, Geisbert TW: Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Feldmann H, Jones SM, Daddario-DiCaprio KM, Geisbert JB, Stroher U, Grolla A, Bray M, Fritz EA, Fernando L, Feldmann F, Hensley LE, Geisbert TW: Effective post-exposure treatment of Ebola infection.
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