A vaccine against Ebola virus would be highly significant in preventing outbreaks which are both naturally occurring or the result of bioterrorist activity. Modifications to previously developed Ebola vaccines were made during the past year to improve expression and immunogenicity. 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 1. 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005079-03
Application #
7592427
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2007
Total Cost
$553,495
Indirect Cost
City
State
Country
United States
Zip Code
Fausther-Bovendo, Hugues; Mulangu, Sabue; Sullivan, Nancy J (2012) Ebolavirus vaccines for humans and apes. Curr Opin Virol 2:324-9
Oswald, Wendelien B; Geisbert, Thomas W; Davis, Kelly J et al. (2007) Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys. PLoS Pathog 3:e9
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
Chandran, Kartik; Sullivan, Nancy J; Felbor, Ute et al. (2005) Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 308:1643-5
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
Sullivan, Nancy J; Peterson, Mary; Yang, Zhi-yong et al. (2005) Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway. J Virol 79:547-53