Safety and Immunogenicity of DNA Vaccines Encoding Ebolavirus and Marburgvirus Wild-type Glycoproteins in a Phase I Clinical Trial

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2014 Sep 17

PMID 25225676

Citations 65

Authors

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

Affiliations

Soon will be listed here.

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.

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