title: Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection.
abstract: The mucosal adjuvant effect of synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [poly(I:C)] against influenza virus was examined under intranasal coadministration with inactivated hemagglutinin (HA) vaccine in BALB/c mice and was shown to have a protective effect against both nasal-restricted infection and lethal lung infection. Intranasal administration of vaccine from PR8 (H1N1) with poly(I:C) induced a high anti-HA immunoglobulin A (IgA) response in the nasal wash and IgG antibody response in the serum, while vaccination without poly(I:C) induced little response. Intracerebral injection confirmed the safety of poly(I:C). In addition, we demonstrated that administration of poly(I:C) with either A/Beijing (H1N1) or A/Yamagata (H1N1) vaccine conferred complete protection against PR8 challenge in this mouse nasal infection model, suggesting that poly(I:C) possessed cross-protection ability against variant viruses. To investigate the mechanism of the protective effect of poly(I:C), mRNA levels of Toll-like receptors and cytokines were examined in the nasal-associated lymphoid tissue after vaccination or virus challenge. Intranasal administration of HA vaccine with poly(I:C) up-regulated expression of Toll-like receptor 3 and alpha/beta interferons as well as Th1- and Th2-related cytokines. We propose that poly(I:C) is a new effective intranasal adjuvant for influenza virus vaccine.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ichinohe
authors.forename: Izumi
authors.initials: I
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Masami
authors.initials: M
authors.lastname: Moriyama
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tamura
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
authors.forename: Joe
authors.initials: J
authors.lastname: Chiba
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurata
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D003429:Cross Reactions; D016207:Cytokines / Q000235:genetics; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000008:administration & dosage; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011070:Poly I-C / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D012449:Safety; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D015854:Up-Regulation
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007252:Influenza Vaccines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D011070:Poly I-C