title: A vaccine prepared from a non-pathogenic H5N1 avian influenza virus strain confers protective immunity against highly pathogenic avian influenza virus infection in cynomolgus macaques.
abstract: In order to prepare for the emergence of pandemic influenza viruses, we have established an influenza virus library that contains non-pathogenic influenza A virus strains with 135 combinations of 15 hemagglutinin and 9 neuraminidase subtypes. In this study, we developed a vaccine against H5N1 highly pathogenic avian influenza (HPAI) virus infection in humans using a virus strain selected from the library. We examined its immunogenic potency using cynomolgus macaques as a primate model. Virus antigen-specific antibodies were elicited by intranasal or subcutaneous administration of inactivated whole virus particle vaccines. After challenge with an H5N1 HPAI virus isolate obtained from a Vietnamese patient, the virus was detected only on next day following inoculation in the nasal and/or tracheal swabs of vaccinated macaques that were asymptomatic. On the other hand, the viruses were isolated from nasal and tracheal swabs from non-vaccinated macaques until day 5 and day 7 after inoculation of the H5N1 HPAI virus, respectively. Although six non-vaccinated macaques developed a high body temperature, and two of them lost their appetite after HPAI virus infection, they recovered by the end of the 12-day observation period and did not show the severe symptoms that have been reported in human H5N1 virus infection cases. This demonstrates that the vaccine prepared with the non-pathogenic H5N1 virus from our influenza virus library conferred protective immunity against H5N1 HPAI virus infection to macaques.
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Itoh
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Ozaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Okamoto
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Torii
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D002642:Chick Embryo; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D053125:Influenza A Virus, H5N2 Subtype / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated