A chimeric Sindbis-based vaccine protects cynomolgus macaques against a lethal aerosol challenge of eastern equine encephalitis virus

Chad J. Roy, A. Paige Adams, Eryu Wang, Grace Leal, Robert L. Seymour, Satheesh K. Sivasubramani, William Mega, Ilya Frolov, Peter J. Didier, Scott C. Weaver

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Eastern equine encephalitis virus (EEEV) is a mosquito-borne alphavirus that causes sporadic, often fatal disease outbreaks in humans and equids, and is also a biological threat agent. Two chimeric vaccine candidates were constructed using a cDNA clone with a Sindbis virus (SINV) backbone and structural protein genes from either a North (SIN/NAEEEV) or South American (SIN/SAEEEV) strain of EEEV. The vaccine candidates were tested in a nonhuman primate (NHP) model of eastern equine encephalitis (EEE). Cynomolgus macaques were either sham-vaccinated, or vaccinated with a single dose of either SIN/NAEEEV or SIN/SAEEEV. After vaccination, animals were challenged by aerosol with a virulent North American strain of EEEV (NA EEEV). The SIN/NAEEEV vaccine provided significant protection, and most vaccinated animals survived EEEV challenge (82%) with little evidence of disease, whereas most SIN/SAEEEV-vaccinated (83%) and control (100%) animals died. Protected animals exhibited minimal changes in temperature and cardiovascular rhythm, whereas unprotected animals showed profound hyperthermia and changes in heart rate postexposure. Acute inflammation and neuronal necrosis were consistent with EEEV-induced encephalitis in unprotected animals, whereas no encephalitis-related histopathologic changes were observed in the SIN/NAEEEV-vaccinated animals. These results demonstrate that the chimeric SIN/NAEEEV vaccine candidate protects against an aerosol EEEV exposure.

Original languageEnglish (US)
Pages (from-to)1464-1470
Number of pages7
JournalVaccine
Volume31
Issue number11
DOIs
StatePublished - Jan 24 2013

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Keywords

  • Aerosol
  • Alphavirus
  • Encephalitis
  • Nonhuman primate
  • 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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