title: A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal West Nile virus infection in aged mice.
abstract: West Nile virus (WNV) is an emerging pathogen that is now the leading cause of mosquito-borne and epidemic encephalitis in the United States. In humans, a small percentage of infected individuals develop severe neuroinvasive disease, with the greatest relative risk being in the elderly and immunocompromised, two populations that are difficult to immunize effectively with vaccines. While inactivated and subunit-based veterinary vaccines against WNV exist, currently there is no vaccine or therapy available to prevent or treat human disease. Here, we describe the generation and preclinical efficacy of a hydrogen peroxide (H(2)O(2))-inactivated WNV Kunjin strain (WNV-KUNV) vaccine as a candidate for further development. Both young and aged mice vaccinated with H(2)O(2)-inactivated WNV-KUNV produced robust adaptive B and T cell immune responses and were protected against stringent and lethal intracranial challenge with a heterologous virulent North American WNV strain. Our studies suggest that the H(2)O(2)-inactivated WNV-KUNV vaccine is safe and immunogenic and may be suitable for protection against WNV infection in vulnerable populations.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Amelia K
authors.initials: AK
authors.lastname: Pinto
authors.forename: Justin M
authors.initials: JM
authors.lastname: Richner
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Poore
authors.forename: Pradnya P
authors.initials: PP
authors.lastname: Patil
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Amanna
authors.forename: Mark K
authors.initials: MK
authors.lastname: Slifka
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004202:Disinfectants / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D038301:Virus Inactivation; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology*
chemical_list: D004202:Disinfectants; D015164:Vaccines, Inactivated; D053060:West Nile Virus Vaccines; D006861:Hydrogen Peroxide