Second generation inactivated eastern equine encephalitis virus vaccine candidates protect mice against a lethal aerosol challenge

PLoS One. 2014 Aug 12;9(8):e104708. doi: 10.1371/journal.pone.0104708. eCollection 2014.

Abstract

Currently, there are no FDA-licensed vaccines or therapeutics for eastern equine encephalitis virus (EEEV) for human use. We recently developed several methods to inactivate CVEV1219, a chimeric live-attenuated eastern equine encephalitis virus (EEEV). Dosage and schedule studies were conducted to evaluate the immunogenicity and protective efficacy of three potential second-generation inactivated EEEV (iEEEV) vaccine candidates in mice: formalin-inactivated CVEV1219 (fCVEV1219), INA-inactivated CVEV1219 (iCVEV1219) and gamma-irradiated CVEV1219 (gCVEV1219). Both fCVEV1219 and gCVEV1219 provided partial to complete protection against an aerosol challenge when administered by different routes and schedules at various doses, while iCVEV1219 was unable to provide substantial protection against an aerosol challenge by any route, dose, or schedule tested. When evaluating antibody responses, neutralizing antibody, not virus specific IgG or IgA, was the best correlate of protection. The results of these studies suggest that both fCVEV1219 and gCVEV1219 should be evaluated further and considered for advancement as potential second-generation inactivated vaccine candidates for EEEV.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Azides / chemistry
  • Encephalitis Virus, Eastern Equine / classification
  • Encephalitis Virus, Eastern Equine / immunology*
  • Encephalomyelitis, Equine / immunology*
  • Encephalomyelitis, Equine / prevention & control
  • Female
  • Formaldehyde / chemistry
  • Gamma Rays
  • Immunity, Mucosal / immunology
  • Mice
  • Mice, Inbred BALB C
  • Vaccination
  • Vaccines, Attenuated / immunology
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Azides
  • Vaccines, Attenuated
  • Viral Vaccines
  • Formaldehyde
  • iodonaphthylazide

Grants and funding

This work was funded by the Defense Threat Reduction Agency (DTRA) Project Number H.H.0003_07_RD_B. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.