A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus

PLoS Negl Trop Dis. 2011 Aug;5(8):e1275. doi: 10.1371/journal.pntd.0001275. Epub 2011 Aug 9.

Abstract

Background: Human outbreaks of Ebola virus (EBOV) are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV) is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes.

Methodology/principal findings: We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV) vector expressing a CD8+ T cell epitope from the nucleoprotein (NP) of Zaire ebolavirus (ZEBOV) (MCMV/ZEBOV-NP(CTL)). MCMV/ZEBOV-NP(CTL) induced high levels of long-lasting (>8 months) CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection.

Conclusions/significance: This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Drug Carriers
  • Ebola Vaccines / administration & dosage
  • Ebola Vaccines / immunology*
  • Ebolavirus / genetics
  • Ebolavirus / immunology*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Genetic Vectors
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Muromegalovirus / genetics*
  • Muromegalovirus / growth & development
  • Nucleoproteins / genetics
  • Nucleoproteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology*

Substances

  • Drug Carriers
  • Ebola Vaccines
  • Epitopes, T-Lymphocyte
  • Nucleoproteins
  • Vaccines, Subunit
  • Vaccines, Synthetic