Chimpanzee Adenovirus Vector Ebola Vaccine - Preliminary Report
Journal Article
Authors:
Ledgerwood, J.;
DeZure, A.;
Stanley, D.;
Novik, L.;
Enama, M.;
Berkowitz, N.;
Hu, Z.;
Joshi, G.;
Ploquin, A.;
Sitar, S.;
Gordon, I.;
Plummer, S.;
Holman, L.;
, ;
Mascola, J.;
Koup, R.;
Sullivan, N.;
Graham, B.;
Team, T.V.R.C. 207 St
Secondary:
N Engl J Med
URL:
http://www.ncbi.nlm.nih.gov/pubmed/25426834
Abstract:
Background The unprecedented 2014 epidemic of Ebola virus disease (EVD) has prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3-vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation. Methods We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2x1010 particle units or 2x1011 particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 4 weeks after vaccination. Results In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2x1011 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2x1011 particle-unit dose than in the group that received the 2x1010 particle-unit dose (geometric mean titer against the Zaire antigen, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2x1011 particle-unit dose than among those who received the 2x1010 particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07). Conclusions Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2x1011 particle-unit dose, glycoprotein Zaire-specific antibody responses were in the range reported to be associated with vaccine-induced protective immunity in challenge studies involving nonhuman primates.
