title: Second generation inactivated eastern equine encephalitis virus vaccine candidates protect mice against a lethal aerosol challenge.
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.
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United States of America; Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.
authors.forename: Shelley P
authors.initials: SP
authors.lastname: Honnold
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United States of America.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Bakken
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United States of America.
authors.forename: Diana
authors.initials: D
authors.lastname: Fisher
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United States of America.
authors.forename: Cathleen M
authors.initials: CM
authors.lastname: Lind
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United States of America.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Cohen
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United States of America.
authors.forename: Lori T
authors.initials: LT
authors.lastname: Eccleston
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United States of America.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Spurgers
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America.
authors.forename: Radha K
authors.initials: RK
authors.lastname: Maheshwari
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United States of America.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Glass
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001386:Azides / Q000737:chemistry; D004663:Encephalitis Virus, Eastern Equine / Q000145:classification / Q000276:immunology*; D004683:Encephalomyelitis, Equine / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D005557:Formaldehyde / Q000737:chemistry; D005720:Gamma Rays; D018928:Immunity, Mucosal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D001386:Azides; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D005557:Formaldehyde; C015298:iodonaphthylazide