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

Yoshimi Tsuda, Patrizia Caposio, Christopher J. Parkins, Sara Botto, Ilhem Messaoudi, Luka Cicin-Sain, Heinz Feldmann, Michael A. Jarvis

Research output: Contribution to journalArticle

59 Citations (Scopus)

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-NPCTL). MCMV/ZEBOV-NPCTL 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.

Original languageEnglish (US)
Article numbere1275
JournalPLoS Neglected Tropical Diseases
Volume5
Issue number8
DOIs
StatePublished - Aug 2011

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Cytomegalovirus Vaccines
Ebolavirus
Nucleoproteins
Epitopes
Democratic Republic of the Congo
Cytomegalovirus
Vaccines
Hominidae
Ebola Vaccines
Gorilla gorilla
Muromegalovirus
Population
Central Africa
T-Lymphocytes
T-Lymphocyte Epitopes
Cytoprotection
Pan troglodytes
Health Services Needs and Demand

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus. / Tsuda, Yoshimi; Caposio, Patrizia; Parkins, Christopher J.; Botto, Sara; Messaoudi, Ilhem; Cicin-Sain, Luka; Feldmann, Heinz; Jarvis, Michael A.

In: PLoS Neglected Tropical Diseases, Vol. 5, No. 8, e1275, 08.2011.

Research output: Contribution to journalArticle

Tsuda, Yoshimi ; Caposio, Patrizia ; Parkins, Christopher J. ; Botto, Sara ; Messaoudi, Ilhem ; Cicin-Sain, Luka ; Feldmann, Heinz ; Jarvis, Michael A. / A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus. In: PLoS Neglected Tropical Diseases. 2011 ; Vol. 5, No. 8.
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