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

Autor:	Sarwar UN; Vaccine Research Center., Costner P; Vaccine Research Center., Enama ME; Vaccine Research Center., Berkowitz N; Vaccine Research Center., Hu Z; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland., Hendel CS; Vaccine Research Center., Sitar S; Vaccine Research Center., Plummer S; Vaccine Research Center., Mulangu S; Vaccine Research Center., Bailer RT; Vaccine Research Center., Koup RA; Vaccine Research Center., Mascola JR; Vaccine Research Center., Nabel GJ; Vaccine Research Center., Sullivan NJ; Vaccine Research Center., Graham BS; Vaccine Research Center., Ledgerwood JE; Vaccine Research Center.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2015 Feb 15; Vol. 211 (4), pp. 549-57. Date of Electronic Publication: 2014 Sep 14.
DOI:	10.1093/infdis/jiu511
Abstrakt:	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. (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.)
Databáze:	MEDLINE
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