Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Nairobi, Kenya

J Infect Dis. 2019 Jun 5;220(1):57-67. doi: 10.1093/infdis/jiz071.

Abstract

Background: During the 2014 West African Ebola outbreak, Ebola vaccine development was accelerated. The phase 1 VAC52150EBL1003 study was performed to investigate 2-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo in an African population located in a high-altitude setting in Nairobi, Kenya.

Methods: Healthy adult volunteers were randomized to receive one of four 2-dose vaccination schedules. The first vaccination was administered at baseline (Ad26.ZEBOV or MVA-BN-Filo), followed by the second vaccination with the alternate vaccine after either 28 or 56 days. Each schedule had a placebo comparator group. The primary objective was to assess the safety and tolerability of these regimens.

Results: Seventy-two volunteers were randomized into 4 groups of 18 (15 received vaccine, and 3 received placebo). The most frequent solicited systemic adverse event was headache (frequency, 50%, 61%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). The most frequent solicited local AE was injection site pain (frequency, 78%, 63%, and 33% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). No differences in adverse events were observed among the different vaccine regimens. High levels of binding and neutralizing anti-Ebola virus glycoprotein antibodies were induced by all regimens and sustained to day 360 after the first dose.

Conclusions: Two-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo was well tolerated and highly immunogenic against Ebola virus glycoprotein.

Clinical trials registration: NCT02376426.

Keywords: Ad26.ZEBOV; Ebola vaccine; MVA-BN-Filo; heterologous 2-dose; safety and immunogenicity.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / immunology
  • Disease Outbreaks / prevention & control
  • Ebola Vaccines / adverse effects*
  • Ebola Vaccines / immunology*
  • Ebolavirus / immunology*
  • Female
  • Healthy Volunteers
  • Hemorrhagic Fever, Ebola / immunology*
  • Hemorrhagic Fever, Ebola / virology
  • Humans
  • Kenya
  • Male
  • Middle Aged
  • Vaccination / adverse effects
  • Vaccines, DNA
  • Viral Vaccines / immunology*
  • Young Adult

Substances

  • Antibodies, Viral
  • Ebola Vaccines
  • MVA vaccine
  • Vaccines, DNA
  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT02376426