IRES-based Venezuelan equine encephalitis vaccine candidate elicits protective immunity in mice

Venezuelan equine encephalitis virus (VEEV) is an arbovirus that causes periodic outbreaks that impact equine and human populations in the Americas. One of the VEEV subtypes located in Mexico and Central America (IE) has recently been recognized as an important cause of equine disease and death, and human exposure also appears to be widespread. Here, we describe the use of an Internal Ribosome Entry Site (IRES) from encephalomyocarditis virus to stably attenuate VEEV, creating a vaccine candidate independent of unstable point mutations. Mice infected with this virus produced antibodies and were protected against lethal VEEV challenge. This IRES-based vaccine was unable to establish productive infection in mosquito cell cultures or in intrathoracically injected Aedes taeniorhynchus, demonstrating that it cannot be transmitted from a vaccinee. These attenuation, efficacy and safety results justify further development for humans or equids of this new VEEV vaccine candidate.

► VEEV genomes containing an EMCV IRES (VEEV/IRES) are attenuated in vitro.
► Mice tolerate VEEV/IRES vaccines well with no signs of illness.
► VEEV/IRES-vaccinated mice are protected against lethal wt VEEV infection.
► VEEV/IRES vaccines are unable to replicate in mosquitoes or mosquito cells.