Can understanding the virulence mechanisms of RNA viruses lead us to a vaccine against eastern equine encephalitis virus and other alphaviruses?

Eastern equine encephalitis virus (EEEV) is a highly neurovirulent mosquito-borne alphavirus that causes severe morbidity and mortality upon human infection. Recent emergence of EEEV into nonendemic regions in the USA and Panama demonstrates the need for the development of an effective EEEV vaccine for licensure for human use. The current EEEV vaccine is available to only at-risk laboratory workers but is poorly immunogenic and requires multiple boosters. In this editorial, we summarize recent developments in understanding alphavirus virulence mechanisms that could be utilized to rationally design a live attenuated vaccine against EEEV or other alphaviruses.