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.