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.
Institute of Human Infection and Immunity, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555-0610, USA. slrossi@utmb.edu
Shannan L
SL
Rossi
Mathilde
M
Guerbois
Rodion
R
Gorchakov
Kenneth S
KS
Plante
Naomi L
NL
Forrester
Scott C
SC
Weaver
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000276:immunology*; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology / Q000517:prevention & control*; D004686:Encephalomyocarditis virus / Q000235:genetics; D051379:Mice; D014176:Protein Biosynthesis; D016019:Survival Analysis; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines