Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial

作者：ElSherif May S; Brown Catherine; MacKinnon Cameron Donna; Li Li; Racine Trina; Alimonti Judie; Rudge Thomas L; Sabourin Carol; Silvera Peter; Hooper Jay W; Kwilas Steven A; Kilgore Nicole; Badorrek Christopher; Ramsey W Jay; Heppner D Gray; Kemp Tracy; Monath Thomas P; Nowak Teresa; McNeil Shelly A; Langley Joanne M; Halperin Scott A^*

来源：Canadian Medical Association Journal, 2017, 189(24): E819-E827.

DOI：10.1503/cmaj.170074

BACKGROUND: The 2013-2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSV Delta G-ZEBOV-GP) was evaluated in humans.
METHODS: In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18-65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo. Follow-up visits spanned 180 days postvaccination for safety monitoring, immunogenicity testing and any rVSV virus shedding.
RESULTS: Forty participants were injected with rVSV Delta G-ZEBOV-GP vaccine (n = 30) or saline placebo (n = 10). No serious adverse events related to the vaccine or participant withdrawals were reported. Solicited adverse events during the 14-day follow-up period were mild to moderate and self-limited, with the exception of injection-site pain and headache. Viremia following vaccination was transient and no longer detectable after study day 3, with no virus shedding in saliva or urine. All vaccinated participants developed serum immunoglobulin G (IgG), as measured by Ebola virus envelope glycoprotein-based enzyme-linked immunosorbent assay (ELISA). Immunogenicity was comparable across all dose groups, and sustained IgG titers were detectable through to the last visit, at study day 180.
INTERPRETATION: In this phase 1 study, there were no safety concerns after a single dose of rVSV Delta G-ZEBOV-GP vaccine. IgG ELISA showed persistent high titers at 180 days postimmunization. There was a period of reactogenicity, but in general, the vaccine was well tolerated. This study provides evidence of the safety and immunogenicity of rVSV Delta G-ZEBOV-GP vaccine and importance of its further investigation.

• 出版日期2017-6-19