title: Mucosal vaccination approach against mosquito-borne Japanese encephalitis virus.
abstract: To investigate the potential applicability of mucosal vaccines against mucosa-unrelated pathogens, a non-parenteral vaccination approach was taken as a prophylactic strategy against mosquito-borne Japanese encephalitis virus (JEV). Intranasal (i.n.) immunization with a mouse brain-derived formalin-inactivated JE vaccine induced a robust virus-neutralizing antibody in mice, and this induction was augmented by co-administration with cholera toxin (CT) and pertussis toxin, but not with killed Bordetella pertussis. The antibody response induced by the i.n. administration of the JE vaccine with bacterial toxins was comparable in intensity to that induced by a parenteral immunization regime, and the former was considerably more effective in terms of delayed-type hypersensitivity and local antibody response. In addition, the adjuvant effects of bacterial toxins were much more prominent for the mucosal than the parenteral route. Two other non-invasive routes, oral and transcutaneous administration, were examined, but the i.n. route was by far the most effective. Finally, the vaccine efficacy of a chimeric fusion protein between the B subunit of CT and the JEV envelope protein showed some promise for the development of non-invasive JE vaccine. Our results suggest that the mucosal vaccination approach is feasible for a non-mucosal pathogen such as JEV, but that the adjuvant, carrier molecule, and administration route must be optimized for construction of an effective vaccine platform.
authors.affiliation: Biochemistry and Applied Biosciences, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima 890-0065, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Harakuni
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kohama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tadano
authors.forename: Gen-Ichiro
authors.initials: G
authors.lastname: Uechi
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Tsuji
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Oku
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D007117:Immunization, Secondary; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D009500:Neutralization Tests; D037342:Pertussis Toxin / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D022321:Japanese Encephalitis Vaccines; D011994:Recombinant Proteins; D002772:Cholera Toxin; D037342:Pertussis Toxin