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

J Infect Dis. 2019 Jun 5;220(1):46-56. doi: 10.1093/infdis/jiz070.

Abstract

Background: Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings.

Methods: Healthy volunteers aged 18-50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days.

Results: Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%-100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination.

Conclusions: Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers.

Clinical trials registration: NCT02376400.

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, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antibody Formation / 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
  • Male
  • Middle Aged
  • Tanzania
  • Uganda
  • Vaccination / adverse effects
  • Viral Vaccines / adverse effects
  • Viral Vaccines / immunology*
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT02376400