title: Induction of cytotoxic T-lymphocyte and antibody responses against highly pathogenic avian influenza virus infection in mice by inoculation of apathogenic H5N1 influenza virus particles inactivated with formalin.
abstract: We investigated whether a vaccine derived from an apathogenic reassortant type A H5N1 influenza strain could induce immune responses in vivo that mediated protection from highly pathogenic avian influenza virus infection in mice. After two subcutaneous immunizations with formalin-inactivated H5N1 whole virus particles (whole particle vaccine), significant killing specific for cells presenting a nucleoprotein peptide from the vaccine strain of the virus was observed. Similar vaccination with viruses treated with ether and formalin, which are commonly used for humans as ether-split vaccines, induced little or no cytotoxic T-cell response. Furthermore, whole particle vaccines of the apathogenic H5N1 strain were more effective than ether-split vaccines at inducing antibody production able to neutralize a highly pathogenic H5N1 strain. Finally, whole particle vaccines of H5N1 protected mice against infection by an H5N1 highly pathogenic avian influenza virus more effectively than did ether-split vaccines. These results suggest that formalin-inactivated virus particles of apathogenic strains are effective for induction of both cytotoxic T-lymphocyte and antibody responses against highly pathogenic avian influenza viruses in vivo, resulting in protection from infection by a highly pathogenic H5N1 virus.
authors.affiliation: Department of Pathology, Shiga University of Medical Sciences, Setatsukinowa, Otsu, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sawai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Itoh
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Ozaki
authors.forename: Norikazu
authors.initials: N
authors.lastname: Isoda
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Okamoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kashima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000918:Antibody Specificity; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005557:Formaldehyde; D005620:Freund's Adjuvant; D007074:Immunoglobulin G / Q000096:biosynthesis; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D016898:Interferon-alpha; D015164:Vaccines, Inactivated; D005557:Formaldehyde; D005620:Freund's Adjuvant