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

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 e...

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Bibliographic Details
Published in:PloS one 2014-08, Vol.9 (8), p.e104708-e104708
Main Authors: Honnold, Shelley P, Bakken, Russell R, Fisher, Diana, Lind, Cathleen M, Cohen, Jeffrey W, Eccleston, Lori T, Spurgers, Kevin B, Maheshwari, Radha K, Glass, Pamela J
Format: Article
Language:English
Subjects:
Aerosols
Animals
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Azides - chemistry
Biology and life sciences
Clinical trials
Cloning
Eastern equine encephalitis
Encephalitis
Encephalitis Virus, Eastern Equine - classification
Encephalitis Virus, Eastern Equine - immunology
Encephalomyelitis, Equine - immunology
Encephalomyelitis, Equine - prevention & control
Female
Formaldehyde - chemistry
Gamma Rays
Gene expression
Glycoproteins
Health sciences
Horses
Immunity, Mucosal - immunology
Immunogenicity
Immunoglobulin A
Immunoglobulin G
Infections
Infectious diseases
Influenza
Medical research
Medicine and Health Sciences
Mice
Mice, Inbred BALB C
Mutation
Proteins
Schedules
Vaccination
Vaccines
Vaccines, Attenuated - immunology
Viral Vaccines - immunology
Virology
Viruses
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0104708