A vaccine candidate for eastern equine encephalitis virus based on IRES-mediated attenuation

Jyotsna Pandya, Rodion Gorchakov, Eryu Wang, Grace Leal, Scott C. Weaver

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 104 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.

Original languageEnglish (US)
Pages (from-to)1276-1282
Number of pages7
JournalVaccine
Volume30
Issue number7
DOIs
StatePublished - Feb 8 2012

Keywords

  • Alphavirus
  • Attenuation
  • Eastern equine encephalitis virus
  • RNA virus
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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