title: Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection.
abstract: Attenuated recombinant H5N1 influenza virus was constructed to develop a safe H5N1 influenza vaccine. The immunogenicity and protective effect of the vaccine prepared from haemagglutinin-modified recombinant H5N1 influenza virus was evaluated in mice intranasally co-administered with cholera toxin B subunit containing a trace amount of holotoxin (CTB*), synthetic double-stranded RNA, poly (I:C) or chitin microparticles (CMP) as adjuvants. Intranasal administration of recombinant H5 HA split vaccine with CTB* or poly(I:C) and/or CMP elicited an immunological response with both anti-H5 HA IgA in the nasal wash and anti-H5 HA IgG antibody in the serum, and showed a protective against lethal H5N1 A/Hong Kong/483/97 (HK483) infection. We also demonstrated that intranasal co-administration of antigen with both poly (I:C) and CMP enhanced the expression of Toll-like receptor (TLR) 3, TLR7 in the spleen. These results indicate that poly (I:C) and CMP are highly effective as mucosal adjuvants for use with the nasal H5N1 vaccine.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Asahi-Ozaki
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Itamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ichinohe
authors.forename: Peter
authors.initials: P
authors.lastname: Strong
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: Masami
authors.initials: M
authors.lastname: Moriyama
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurata
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis* / Q000097:blood; D002686:Chitin / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009297:Nasal Mucosa / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D011070:Poly I-C / Q000276:immunology; D012330:RNA, Double-Stranded / Q000276:immunology; D013154:Spleen / Q000276:immunology; D051193:Toll-Like Receptors / Q000096:biosynthesis; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D012330:RNA, Double-Stranded; D051193:Toll-Like Receptors; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C483468:hemagglutinin, human influenza A virus; D002686:Chitin; D002772:Cholera Toxin; D011070:Poly I-C