• Uzma N Sarwar, Pamela Costner, Mary E Enama, Nina Berkowitz, Zonghui Hu, Cynthia S Hendel, Sandra Sitar, Sarah Plummer, Sabue Mulangu, Robert T Bailer, Richard A Koup, John R Mascola, Gary J Nabel, Nancy J Sullivan, Barney S Graham, Julie E Ledgerwood, and VRC 206 Study Team.
• Vaccine Research Center.
• J. Infect. Dis. 2015 Feb 15; 211 (4): 549-57.

BackgroundEbolavirus 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.MethodsThe 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.ResultsThe 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.ConclusionsThe 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 RegistrationNCT00605514.Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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