Complete protection of the BALB/c and C57BL/6J mice against Ebola and Marburg virus lethal challenges by pan-filovirus T-cell epigraph vaccine

PLoS Pathog. 2019 Feb 28;15(2):e1007564. doi: 10.1371/journal.ppat.1007564. eCollection 2019 Feb.

Abstract

There are a number of vaccine candidates under development against a small number of the most common outbreak filoviruses all employing the virus glycoprotein (GP) as the vaccine immunogen. However, antibodies induced by such GP vaccines are typically autologous and limited to the other members of the same species. In contrast, T-cell vaccines offer a possibility to design a single pan-filovirus vaccine protecting against all known and even likely existing, but as yet unencountered members of the family. Here, we used a cross-filovirus immunogen based on conserved regions of the filovirus nucleoprotein, matrix and polymerase to construct simian adenovirus- and poxvirus MVA-vectored vaccines, and in a proof-of-concept study demonstrated a protection of the BALB/c and C57BL/6J mice against high, lethal challenges with Ebola and Marburg viruses, two distant members of the family, by vaccine-elicited T cells in the absence of GP antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Ebola Vaccines
  • Ebolavirus / pathogenicity
  • Female
  • Filoviridae / immunology*
  • Filoviridae / metabolism
  • Filoviridae / pathogenicity
  • Hemorrhagic Fever, Ebola
  • Immunity, Cellular / immunology
  • Male
  • Marburgvirus / pathogenicity
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Proof of Concept Study
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Viral Vaccines / pharmacology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Ebola Vaccines
  • Viral Vaccines