title: Influenza hemagglutinin vaccine with poly(gamma-glutamic acid) nanoparticles enhances the protection against influenza virus infection through both humoral and cell-mediated immunity.
abstract: Subcutaneous immunization with an influenza hemagglutinin (HA) vaccine can induce the production of virus-neutralizing antibodies, but not a cell-mediated immune response. Here we tested whether amphiphilic poly(gamma-glutamic acid)-graft-l-phenylalanine copolymers (gamma-PGA-NPs), which are derived from a bacterial capsular exopolymer produced by certain Bacillus natto strains, were an effective adjuvant for systemic influenza HA vaccination. Subcutaneous immunization with a mixture of HA vaccine and gamma-PGA-NPs induced higher mononuclear cell proliferation and the production of gamma-interferon (IFN-gamma), interleukin (IL)-4, and IL-6 upon HA restimulation, and enhanced not only anti-HA neutralizing antibody production but also the influenza virus-specific cell-mediated immune response, including CTL activity, compared with immunization with HA alone or a mixture of HA and aluminum adjuvant. HA vaccine with gamma-PGA-NPs protected mice against challenges with lethal doses of homologous influenza virus. The results indicate that adding gamma-PGA-NPs to the HA vaccine promotes effective protection and identifies gamma-PGA-NPs as a new, effective, and potent candidate adjuvant for a subcutaneous influenza virus vaccine.
authors.affiliation: Laboratory of Virology and Vaccinology, Division of Biomedical Research, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Hironori
authors.initials: H
authors.lastname: Yoshii
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Okuno
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamanishi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007114:Immunization; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011099:Polyglutamic Acid; D007371:Interferon-gamma