Abstract

Use of the FDA Animal Rule for licensure of Ebola and Marburg virus vaccines requires a detailed understanding of vaccine-induced immune response since correlates of immunity will replace efficacy studies that would otherwise be provided to support vaccine licensure. An immune correlate of protection against infection must first be identified in an animal model that reasonably represents disease pathogenesis in humans. Vaccine efficacy is tested in animals, and the immune response that correlates best with survival is identified. Subsequent immunogenicity studies in human subjects are designed to test whether the vaccine can induce similar responses in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI005082-07
Application #
8336400
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2011
Total Cost
$901,608
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Fausther-Bovendo, Hugues; Mulangu, Sabue; Sullivan, Nancy J (2012) Ebolavirus vaccines for humans and apes. Curr Opin Virol 2:324-9
Fabozzi, Giulia; Nabel, Christopher S; Dolan, Michael A et al. (2011) Ebolavirus proteins suppress the effects of small interfering RNA by direct interaction with the mammalian RNA interference pathway. J Virol 85:2512-23
Sullivan, Nancy J; Hensley, Lisa; Asiedu, Clement et al. (2011) CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nat Med 17:1128-31
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
Ledgerwood, J E; Costner, P; Desai, N et al. (2010) A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine 29:304-13
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