A vaccine candidate for eastern equine encephalitis virus based on IRES-mediated attenuation.
To develop an effective vaccine against eastern equine encephalitis (EEE), we engineered a recombinant EEE virus (EEEV) that was attenuated and capable of replicating only in vertebrate cells, an important safety feature for live vaccines against mosquito-borne viruses. The subgenomic promoter was inactivated with 13 synonymous mutations and expression of the EEEV structural proteins was placed under the control of an internal ribosomal entry site (IRES) derived from encephalomyocarditis virus (EMCV). We tested this vaccine candidate for virulence, viremia and efficacy in the murine model. A single subcutaneous immunization with 10(4) infectious units protected 100% of mice against intraperitoneal challenge with a highly virulent North American EEEV strain. None of the mice developed any signs of disease or viremia after immunization or following challenge. Our findings suggest that the IRES-based attenuation approach can be used to develop a safe and effective vaccine against EEE and other alphaviral diseases.
Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, Center for Biodefense and Emerging Infectious Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, United States.
Jyotsna
J
Pandya
Rodion
R
Gorchakov
Eryu
E
Wang
Grace
G
Leal
Scott C
SC
Weaver
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001483:Base Sequence; D004663:Encephalitis Virus, Eastern Equine / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D020242:Encephalomyelitis, Eastern Equine / Q000276:immunology / Q000517:prevention & control*; D004686:Encephalomyocarditis virus / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D005818:Genetic Engineering / Q000379:methods; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000235:genetics* / Q000276:immunology; D012270:Ribosomes / Q000235:genetics; D014611:Vaccination; D014613:Vaccines, Attenuated; D014765:Viral Vaccines / Q000008:administration & dosage; D014766:Viremia / Q000276:immunology / Q000517:prevention & control*; D014774:Virulence
D000914:Antibodies, Viral; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines