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

CMAJ. 2017 Jun 19;189(24):E819-E827. doi: 10.1503/cmaj.170074.

Abstract

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 (rVSVΔG-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 rVSVΔG-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 rVSVΔG-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 rVSVΔG-ZEBOV-GP vaccine and importance of its further investigation. Trial registration: Clinical-Trials.gov no., NCT02374385.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Canada
  • Double-Blind Method
  • Ebola Vaccines / administration & dosage*
  • Ebolavirus
  • Female
  • Healthy Volunteers
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Middle Aged
  • Regression Analysis
  • Vaccination / methods
  • Vaccines, Synthetic / administration & dosage
  • Vesicular stomatitis Indiana virus
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Ebola Vaccines
  • G protein, vesicular stomatitis virus
  • Immunoglobulin G
  • Membrane Glycoproteins
  • Vaccines, Synthetic
  • Viral Envelope Proteins

Associated data

  • ClinicalTrials.gov/NCT02374385