Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial.
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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.Clinical trials registration
NCT00605514.
SUBMITTER: Sarwar UN
PROVIDER: S-EPMC4318920 | biostudies-literature |
REPOSITORIES: biostudies-literature
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