Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial.

Publication Type
Journal Article
Year of Publication
Sarwar, Uzma N; Costner, Pamela; Enama, Mary E; Berkowitz, Nina; Hu, Zonghui; Hendel, Cynthia S; Sitar, Sandra; Plummer, Sarah; Mulangu, Sabue; Bailer, Robert T; Koup, Richard A; Mascola, John R; Nabel, Gary J; Sullivan, Nancy J; Graham, Barney S; Ledgerwood, Julie E; VRC 206 Study Team
J Infect Dis
Date Published
2015 Feb 15
Adult; Antibodies, Viral; Cytokines; Ebola Vaccines; Ebolavirus; Enzyme-Linked Immunospot Assay; Female; Humans; Male; Marburgvirus; Middle Aged; T-Lymphocytes; Vaccines, DNA; Viral Vaccines; Young Adult

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.