부산대학교 도서관

Venezuelan equine encephalitis virus (VEEV) is an arbovirus endemic to the Americas that is responsible for severe, sometimes fatal, disease in humans and horses. We previously described an IRES-based VEE vaccine candidate based up the IE serotype that offers complete protection against a lethal subtype IE VEEV challenge in mice. Here we demonstrate the IRES-based vaccine's ability to protect against febrile disease in cynomolgus macaques. Vaccination was well tolerated and elicited robust neutralizing antibody titers noticed as early as day 14. Moreover, complete protection from disease characterized by absence of viremia and characteristic fever following aerosolized IE VEEV challenge was observed in all vaccinees compared to control animals, which developed clinical disease. Together, these results highlight the safety and efficacy of IRES-based VEEV vaccine to protect against an endemic, pathogenic VEEV IE serotype. Author Summary: Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne arbovirus endemic to the Americas that affects a wide range of equids and humans. Vaccination has been one of the strategies to combat spread of disease in areas with high rates incidence of VEEV, although existing vaccines have proven less than effective against genetically diverse serotypes. In addition to being a natural vectorborne threat, VEEV is considered a biological threat agent that could be used as a weapon. We evaluated a new Internal Ribosome Entry Site (IRES)-containing chimeric viral vaccine using an advanced nonhuman primate model of VEEV infection. Vaccinated animals showed robust humoral immune responses to a single prime immunization with IE VEEV/IRES vaccine. The vaccine protected against an aerosolized IE (68U201) challenge, with vaccinees showing no blood viremia or development of febrile disease, including no pyrexia associated with VEEV infection. This vaccine product has shown efficacy against serotype-specific challenge model and provides enabling data as the basis for future clinical development. [ABSTRACT FROM AUTHOR]