A Replication Defective Recombinant Ad5 Vaccine Expressing Ebola Virus GP is Safe and Immunogenic in Healthy Adults

Publication Type
Journal Article
Year of Publication
Ledgerwood, JE; Costner, P; Desai, N; Holman, L; Enama, ME; Yamshchikov, G; Mulangu, S; Hu, Z; Andrews, CA; Sheets, RA; Koup, RA; Roederer, M; Bailer, R; Mascola, JR; Pau, MG; Sullivan, NJ; Goudsmit, J; Nabel, GJ; Graham, BS; The VRC 205 Study Team
Start Page
Date Published
Adenoviruses; Antibodies; Ebola Vaccines; Ebolavirus/genetics/immunology; Neutralizing/blood Antibodies; Viral/blood Cytokines/immunology
Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2x10(9) (n=12), or 2x10(10) (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.