A Replication Defective Recombinant Ad5 Vaccine Expressing Ebola Virus GP is Safe and Immunogenic in Healthy Adults
12/2010
Journal Article
Authors:
Ledgerwood, J.E.;
Costner, P.;
Desai, N.;
Holman, L.;
Enama, M.E.;
Yamshchikov, G.;
Mulangu, S.;
Hu, Z.;
Andrews, C.A.;
Sheets, R.A.;
Koup, R.A.;
Roederer, M.;
Bailer, R.;
, ;
Pau, M.G.;
Sullivan, N.J.;
Goudsmit, J.;
Nabel, G.J.;
Graham, B.S.;
Team, T.V.R.C. 205 St
Secondary:
Vaccine
Volume:
29
Pagination:
304-313
URL:
http://www.ncbi.nlm.nih.gov/pubmed/21034824
Keywords:
Adenoviruses; Antibodies; Ebola Vaccines; Ebolavirus/genetics/immunology; Neutralizing/blood Antibodies; Viral/blood Cytokines/immunology
Abstract:
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.
