title: Intranasal immunization with a formalin-inactivated human influenza A virus whole-virion vaccine alone and intranasal immunization with a split-virion vaccine with mucosal adjuvants show similar levels of cross-protection.
abstract: The antigenicity of seasonal human influenza virus changes continuously; thus, a cross-protective influenza vaccine design needs to be established. Intranasal immunization with an influenza split-virion (SV) vaccine and a mucosal adjuvant induces cross-protection; however, no mucosal adjuvant has been assessed clinically. Formalin-inactivated intact human and avian viruses alone (without adjuvant) induce cross-protection against the highly pathogenic H5N1 avian influenza virus. However, it is unknown whether seasonal human influenza formalin-inactivated whole-virion (WV) vaccine alone induces cross-protection against strains within a subtype or in a different subtype of human influenza virus. Furthermore, there are few reports comparing the cross-protective efficacy of the WV vaccine and SV vaccine-mucosal adjuvant mixtures. Here, we found that the intranasal human influenza WV vaccine alone induced both the innate immune response and acquired immune response, resulting in cross-protection against drift variants within a subtype of human influenza virus. The cross-protective efficacy conferred by the WV vaccine in intranasally immunized mice was almost the same as that conferred by a mixture of SV vaccine and adjuvants. The level of cross-protective efficacy was correlated with the cross-reactive neutralizing antibody titer in the nasal wash and bronchoalveolar fluids. However, neither the SV vaccine with adjuvant nor the WV vaccine induced cross-reactive virus-specific cytotoxic T-lymphocyte activity. These results suggest that the intranasal human WV vaccine injection alone is effective against variants within a virus subtype, mainly through a humoral immune response, and that the cross-protection elicited by the WV vaccine and the SV vaccine plus mucosal adjuvants is similar.
authors.affiliation: Laboratory of Virology and Vaccinology, Division of Biomedical Research, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Sumiko
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takenaka
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: Haredy
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanimoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gomi
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Okuno
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamanishi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D056738:Cross Protection; D005260:Female; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated