title: A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Patrizia
authors.initials: P
authors.lastname: Caposio
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Parkins
authors.forename: Sara
authors.initials: S
authors.lastname: Botto
authors.forename: Ilhem
authors.initials: I
authors.lastname: Messaoudi
authors.forename: Luka
authors.initials: L
authors.lastname: Cicin-Sain
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jarvis
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004337:Drug Carriers; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000276:immunology*; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000235:genetics* / Q000254:growth & development; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D046129:Ebola Vaccines; D018984:Epitopes, T-Lymphocyte; D009698:Nucleoproteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic