Further search for small molecular inactivants capable of eliciting respiratory mucosal immunogenicity by modifying Sendai virus core RNA.
Five groups of 32 chemicals were examined regarding their immunological functions as modifier inactivants to make inactivated Sendai nasal vaccine using a contact exposure experiment, direct immunofluorescent method, and serum HI titer. (1) Five of the nine reactive groups of reactive dyes (2-chloropyridine, 2, 4, 6-trichloropyrimidine, vinylsulfonic acid, epichlorohydrin and beta-chloroethylamine) induced complete or almost complete defense in the entire respiratory tract, and the four other vaccines brought about slight infection in the respiratory tracts. There was no marked rise in serum HI titers post-exposure, despite uneven development. (2) Of the four sizable substituted AS naphthol vaccines, naphthol AS-IRG and AS-G vaccines elicited nearly complete defense, but the two other vaccines, inactivated with more elongated molecules, invited rare and successive infections. The three immune groups produced invariably high serum HI titers. (3) Of the six naphthalene derivative vaccines, two (3-hydroxy-2-naphthoic acid methylester and 2-naphthol-6-sulfonic acid) induced complete or almost complete protection. But two vaccines brought about less protection, and the remaining two vaccines caused heavy infections. (4) Of the six benzene derivative vaccines, both m-nitrobenzenesulfonic acid and isatoic anhydride induced complete protection. Three vaccines permitted slight infections but 2, 4, 6-trinitrobenzenesulfonic acid vaccine caused severe infection. (5) Of the seven food dye vaccines, only orange I induced complete or nearly complete defense, while the other dye vaccines were inferior. In effect, twelve inactivated Sendai nasal vaccines modified the ribose and/or phosphate groups of the virus core RNA through five groups of small-sized molecules with specially fixed side chains, and elicited complete or almost complete respiratory mucosal defense. The viral stabilization requiring the least alteration of the configuration will be involved in the chemical modification.
Miyamae
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Department of Laboratory Animal Medicine, School of Health Sciences, Fujita Health University, Aichi, Japan.
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001555:Benzene Derivatives / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D018928:Immunity, Mucosal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009281:Naphthalenes / Q000494:pharmacology; D009284:Naphthols / Q000494:pharmacology; D009297:Nasal Mucosa / Q000276:immunology; D012367:RNA, Viral / Q000187:drug effects*; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000517:prevention & control; D018108:Respirovirus / Q000235:genetics / Q000276:immunology*; D010253:Respirovirus Infections / Q000276:immunology* / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D001555:Benzene Derivatives; D004396:Coloring Agents; D009281:Naphthalenes; D009284:Naphthols; D012367:RNA, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; C008584:naphthol AS