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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005080-04
Application #
7732775
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2008
Total Cost
$596,210
Indirect Cost
City
State
Country
United States
Zip Code
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Yu, Jae-Sung; Liao, Hua-Xin; Gerdon, Aren E et al. (2006) Detection of Ebola virus envelope using monoclonal and polyclonal antibodies in ELISA, surface plasmon resonance and a quartz crystal microbalance immunosensor. J Virol Methods 137:219-28
Sullivan, Nancy J; Geisbert, Thomas W; Geisbert, Joan B et al. (2006) Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs. PLoS Med 3:e177
Martin, Julie E; Sullivan, Nancy J; Enama, Mary E et al. (2006) A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol 13:1267-77
Jones, Steven M; Feldmann, Heinz; Stroher, Ute et al. (2005) Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med 11:786-90