A vaccine against Marburg virus would be highly significant in preventing outbreaks which are both naturally occurring or the result of bioterrorist activity. To develop a safe and effective vaccine against the Marburg virus. Ebola and Marburg viruses have been identified as the cause of several highly lethal outbreaks of hemorrhagic fever for which there is no effective treatment or cure. Therefore, vaccine studies are critically important for protection against infection. We developed a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of primary immunization with plasmid DNA and boosting with adenoviral vectors containing Ebola genes generated protective immunity in cynomolgus macaques. The vaccine yielded 100% protective efficacy against Ebola infection and showed for the first time that protective immune responses could be generated in primates. The DNA vaccine is currently being tested in Phase I human clinical trials conducted by the VRC Clinical Trials Core Laboratory. In addition to our DNA prime/adenoviral vector boost vaccine studies, our laboratory has demonstrated that protective immunity to Ebola can be generated with a single inoculation of adenoviral vector vaccine 2, a result with significant implications for conducting enhanced ring vaccination during an Ebola outbreak. We have applied a similar strategy to the development of protective vaccines against Marburg virus.

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12
Fiscal Year
2016
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Sarwar, Uzma N; Costner, Pamela; Enama, Mary E et al. (2015) Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial. J Infect Dis 211:549-57
Geisbert, Thomas W; Bailey, Michael; Hensley, Lisa et al. (2011) Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to Ad5 and protect nonhuman primates against ebolavirus challenge. J Virol 85:4222-33
Geisbert, Thomas W; Bailey, Michael; Geisbert, Joan B et al. (2010) Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. J Virol 84:10386-94
Hensley, Lisa E; Mulangu, Sabue; Asiedu, Clement et al. (2010) Demonstration of cross-protective vaccine immunity against an emerging pathogenic Ebolavirus Species. PLoS Pathog 6:e1000904
Shedlock, Devon J; Bailey, Michael A; Popernack, Paul M et al. (2010) Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms. Virology 401:228-35
Sullivan, Nancy J; Martin, Julie E; Graham, Barney S et al. (2009) Correlates of protective immunity for Ebola vaccines: implications for regulatory approval by the animal rule. Nat Rev Microbiol 7:393-400