Venezuelan equine encephalitis virus: novel live-attenuated vaccines for inducing complete protective immunity

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that causes severe neuroinflammation and fatal infections in some people. Numerous outbreaks of VEEV have been reported in Latin America in the past century. Though mosquito-borne, studies have demonstrated that aerosolized VEEV infections lead to significantly higher mortality rates in animal models, suggesting that VEEV, if aerosolized, could cause widespread infections. There are currently no FDA-approved vaccines against VEEV, though TC-83, a live-attenuated strain of VEEV, has been tested as an investigational new drug in laboratory personnel and at-risk health workers. Its use, however, has been associated with severe adverse events and variable immunogenicity. Novel live-attenuated vaccines such as the V4020, V3526, VRC-WEVVLP03-00VP, 68U201/IRES1, and others are under development to overcome some of the limitations associated with the TC-83 vaccine. Here, we discuss the pathogenesis of VEEV and the current state of VEEV vaccines that are in clinical development.