A Replicating Cytomegalovirus-Based Vaccine Encoding a Single Ebola Virus Nucleoprotein CTL Epitope Confers Protection against Ebola Virus.

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. Author Summary: Human outbreaks of hemorrhagic disease caused by Ebola virus (EBOV) are a serious health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans. Candidate EBOV vaccines do not spread from the initial vaccinee. In addition to being highly immunogenic, vaccines based on the cytomegalovirus (CMV) platform have the unique potential to re-infect and disseminate through target populations. To explore the utility of CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV) vector expressing a region of nucleoprotein (NP) of Zaire ebolavirus (ZEBOV) (MCMV/ZEBOV-NPCTL). MCMV/ZEBOV-NPCTL induced high levels of long-lasting CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. The absence of ZEBOV neutralizing and only low, sporadic levels of total anti-ZEBOV IgG antibodies in protected animals prior to ZEBOV challenge indicate a role, albeit perhaps not exclusive, for CD8+ T cells in mediating protection. This study demonstrates the ability of a CMV-based vaccine approach to protect against ZEBOV, and provides a 'proof-of-concept' for the potential for a 'disseminating' CMV-based EBOV vaccine to prevent EBOV transmission in wild animal populations. [ABSTRACT FROM AUTHOR]