Alphaviral Encephalitides

Alphaviruses that typically cause encephalitis include eastern (EEEV), Venezuelan (VEEV), and western equine encephalitis viruses (WEEV). All are important emerging viral pathogens of humans, equids, and other domesticated animals. Although these viruses do not exhibit the high human fatality rates characteristic of some more virulent biothreat viruses, all are highly infectious via the aerosol route and highly incapacitating, making them biothreat agents. Despite vaccine development efforts dating back many decades, licensed human vaccines are not available. Investigational new drug vaccines against VEEV and EEEV are offered to at-risk laboratory workers through the U.S. Army Special Immunizations program. However, these vaccines suffer from reactogenicity and poor rates of seroconversion (VEEV) and poor immunogenicity requiring multiple doses and frequent boosters (EEEV). Veterinary vaccines are widely available in America but most suffer from poor and short-lived immunogenicity, and the risk of residual, virulent virus in inactivated preparations. Recent advances in understanding of molecular aspects of alphavirus pathogenesis and genetics promise improvements in live-attenuated vaccines against all three encephalitis alphaviruses, as well as safer virus strains for inactivated vaccine preparations. Virus-like particles that express either alphavirus or other antigens, based on alphavirus replicon genomes, are also being widely developed as vaccine platforms.