Safety and Immunogenicity of DNA Vaccines Encoding Ebolavirus and Marburgvirus Wild-Type Glycoproteins in a Phase I Clinical Trial
02/2015
Journal Article
Authors:
Sarwar, U.;
Costner, P.;
Enama, M.;
Berkowitz, N.;
Hu, Z.;
Hendel, C.;
Sitar, S.;
Plummer, S.;
Mulangu, S.;
Bailer, R.;
Koup, R.;
Mascola, J.;
Nabel, G.;
Sullivan, N.;
Graham, B.;
Ledgerwood, J.E.;
Team, T.V.R.C. 206 St
Secondary:
J Infect Dis
Volume:
211
Pagination:
549-557
URL:
http://www.ncbi.nlm.nih.gov/pubmed/25225676
Keywords:
Antibodies; Cytokines/blood; DNA; Ebola Vaccines; Ebola virus; filovirus; immunology; Marburg virus; Viral/blood/immunology
Abstract:
BACKGROUND: Ebolavirus and Marburgvirus cause severe hemorrhagic fever with high mortality and are potential bioterrorism agents. There are no available vaccines or therapeutic agents. Previous clinical trials evaluated transmembrane-deleted and point-mutation Ebolavirus glycoproteins (GPs) in candidate vaccines. Constructs evaluated in this trial encode wild-type (WT) GP from Ebolavirus Zaire and Sudan species and the Marburgvirus Angola strain expressed in a DNA vaccine. METHODS: The VRC 206 study evaluated the safety and immunogenicity of these DNA vaccines (4 mg administered intramuscularly by Biojector) at weeks 0, 4, and 8, with a homologous boost at or after week 32. Safety evaluations included solicited reactogenicity and coagulation parameters. Primary immune assessment was done by means of GP-specific enzyme-linked immunosorbent assay. RESULTS: The vaccines were well tolerated, with no serious adverse events; 80% of subjects had positive enzyme-linked immunosorbent assay results (>/=30) at week 12. The fourth DNA vaccination boosted the immune responses. CONCLUSIONS: The investigational Ebolavirus and Marburgvirus WT GP DNA vaccines were safe, well tolerated, and immunogenic in this phase I study. These results will further inform filovirus vaccine research toward a goal of inducing protective immunity by using WT GP antigens in candidate vaccine regimens.
