Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein Nanoparticle Vaccine With Matrix-M Adjuvant in Healthy Adults

J Infect Dis. 2020 Jul 23;222(4):572-582. doi: 10.1093/infdis/jiz518.

Abstract

Background: Ebola virus (EBOV) epidemics pose a major public health risk. There currently is no licensed human vaccine against EBOV. The safety and immunogenicity of a recombinant EBOV glycoprotein (GP) nanoparticle vaccine formulated with or without Matrix-M adjuvant were evaluated to support vaccine development.

Methods: A phase 1, placebo-controlled, dose-escalation trial was conducted in 230 healthy adults to evaluate 4 EBOV GP antigen doses as single- or 2-dose regimens with or without adjuvant. Safety and immunogenicity were assessed through 1-year postdosing.

Results: All EBOV GP vaccine formulations were well tolerated. Receipt of 2 doses of EBOV GP with adjuvant showed a rapid increase in anti-EBOV GP immunoglobulin G titers with peak titers observed on Day 35 representing 498- to 754-fold increases from baseline; no evidence of an antigen dose response was observed. Serum EBOV-neutralizing and binding antibodies using wild-type Zaire EBOV (ZEBOV) or pseudovirion assays were 3- to 9-fold higher among recipients of 2-dose EBOV GP with adjuvant, compared with placebo on Day 35, which persisted through 1 year.

Conclusions: Ebola virus GP vaccine with Matrix-M adjuvant is well tolerated and elicits a robust and persistent immune response. These data suggest that further development of this candidate vaccine for prevention of EBOV disease is warranted.

Keywords: Ebola virus; Matrix-M adjuvant; glycoprotein; nanoparticle vaccine.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Australia
  • Ebola Vaccines / immunology*
  • Female
  • Healthy Volunteers
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Humans
  • Male
  • Nanoparticles / administration & dosage*
  • Safety
  • Saponins / administration & dosage*
  • Vaccination
  • Viral Envelope Proteins / immunology*
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Ebola Vaccines
  • Matrix-M
  • Saponins
  • Viral Envelope Proteins