Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection

Sci Rep. 2017 Apr 20;7(1):919. doi: 10.1038/s41598-017-01032-8.

Abstract

Ebola virus (EBOV) poses a significant threat to human health as highlighted by the recent epidemic in West Africa. Data from animal studies and a ring vaccination clinical trial conducted in Guinea during the recent epidemic demonstrated that a recombinant VSV where G protein is replaced with EBOV GP (rVSV-EBOV) is safe and highly efficacious. We previously established that antibodies are essential for rVSV-EBOV mediated protection against EBOV; however, the mechanisms by which this vaccine induces a humoral response and the role of T-cells in rVSV-EBOV mediated protection remain poorly understood. Since this is the only vaccine platform that has completed Phase III clinical studies, it is imperative to gain a better understanding of its mechanisms of protection. Therefore, we performed a longitudinal gene expression analysis of samples collected from controls and T-cell-depleted macaques after rVSV-EBOV vaccination and EBOV challenge. We show that rVSV-EBOV vaccination induces gene expression changes consistent with anti-viral immunity and B-cell proliferation. We also report a previously unappreciated role for CD8+ T-cells in mediating rVSV-EBOV protection. Finally, limited viral transcription in surviving animals may boost protective responses after EBOV challenge by maintaining transcriptional changes. This study presents a novel approach in determining mechanisms of vaccine efficacy.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • Ebola Vaccines / genetics
  • Ebola Vaccines / immunology*
  • Ebolavirus / genetics
  • Ebolavirus / immunology
  • Hemorrhagic Fever, Ebola / blood
  • Hemorrhagic Fever, Ebola / immunology*
  • Macaca fascicularis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Transcriptome*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • Ebola Vaccines
  • G protein, vesicular stomatitis virus
  • Membrane Glycoproteins
  • Viral Envelope Proteins