Protection Against Marburg Virus Using a Recombinant VSV-Vaccine Depends on T and B Cell Activation

Front Immunol. 2019 Jan 22:9:3071. doi: 10.3389/fimmu.2018.03071. eCollection 2018.

Abstract

Marburg virus (MARV) is the causative agent of hemorrhagic fever outbreaks with high case fatality rates. Closely related to Ebola virus, MARV is a filamentous virus with a negative-sense, single-stranded RNA genome. Although extensive studies on filovirus countermeasures have been conducted, there are no licensed treatments against MARV infections. An experimental vaccine based on the recombinant vesicular stomatitis virus (VSV) expressing the MARV-Musoke glycoprotein demonstrated complete protection when a single dose was administered 28 days and up to 14 months prior to MARV challenge. Here, we analyzed the protective efficacy of an updated vaccine expressing the MARV-Angola glycoprotein (VSV-MARV). A single dose of VSV-MARV given 5 weeks before challenge provided uniform protection with no detectable viremia. The vaccine induced B and T cell proliferation and, importantly, antigen-specific IgG production. Transcriptomic signatures confirm these findings and suggest innate immunity engendered by VSV-MARV may direct the development of protective humoral immunity.

Keywords: MARV Angola; VSV-MARV; filovirus; macaque; nonhuman primate model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Disease Models, Animal
  • Female
  • Humans
  • Lymphocyte Activation*
  • Macaca fascicularis
  • Male
  • Marburg Virus Disease / immunology
  • Marburg Virus Disease / prevention & control*
  • Marburg Virus Disease / virology
  • Marburgvirus / immunology*
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Vesiculovirus / immunology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / immunology
  • Viremia / immunology
  • Viremia / prevention & control*
  • Viremia / virology

Substances

  • GP-protein, Marburg virus
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • Viral Vaccines