Alphavirus virus-based chimeric vaccines against encephalitic alphaviruses

Encephalitic viruses in the Family Togaviridae, genus Alphavirus are zoonotic pathogens that are transmitted via hematophagous arthropods and have a widespread distribution in North, Central and South America and include Venezuelan equine encephalitis virus (VEEV), Western equine encephalitis virus (WEEV), Eastern equine encephalitis virus (EEEV). The deficit in specific antiviral drugs or vaccines for effective treatment or prevention of infection and disease in humans has prompted the development of recombinant live attenuated vaccines utilizing Sindbis virus (SIN), a relatively nonpathogenic alphavirus in humans, as a means for expression all of the structural proteins of the virulent alphaviruses. The safety and efficacy of these chimeric SIN/VEE viruses have been extensively evaluated in animal models, including immunodeficient mice. The epidemiological distribution of these viruses and the disease manifestations are reviewed briefly. Progress in the evaluation of the safety, immunogenicity and efficacy of the SIN/VEEV and SIN/EEEV candidate vaccines against VEEV and EEEV, respectively, as well as chimeric SIN/RVFV vaccine candidates and the potential for elucidation of the mechanism of efficacy employing mice with selective immunodeficiencies is discussed.