title: Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.
abstract: H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus.
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori, 680-8553, Japan.
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Ozaki
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori, 680-8553, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Soda
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ishigaki
authors.affiliation: Laboratory of Microbiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okamatsu
authors.affiliation: Laboratory of Microbiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan.|Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido, 060-0815, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.affiliation: School of Veterinary Medicine, Kitasato University, Towada, Aomori, 034-8628, Japan.
authors.forename: Chun-Ho
authors.initials: CH
authors.lastname: Park
authors.affiliation: Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Laboratory of Microbiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan.|Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido, 060-0815, Japan.|Research Center for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, 001-0020, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.|Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001980:Bronchi / Q000473:pathology; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008221:Lymphoid Tissue / Q000473:pathology; D008252:Macaca fascicularis; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: BALT; H9N2 influenza virus; non-human primate; vaccine; virus library