title: Co-immunization with tandem repeat heterologous M2 extracellular proteins overcomes strain-specific protection of split vaccine against influenza A virus.
abstract: Current influenza vaccines are less efficacious against antigenically different influenza A viruses. This study presents an approach to overcome strain-specific protection, using a strategy of co-immunization with seasonal H3N2 split vaccine and yeast-expressed soluble proteins of a tandem repeat containing heterologous influenza M2 ectodomains (M2e5x). Co-immunization with both vaccines in mice was superior to either vaccine alone in inducing cross protection against heterologous H3N2 virus by raising M2e-specific humoral and cellular immune responses toward a T-helper type 1 profile inducing IgG2a isotype antibodies as well as interferon-γ-producing cells in systemic and mucosal sites. In addition, co-immunization sera were found to confer cross-protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. A mechanistic study provides evidence that activation of dendritic cells by co-stimulation with M2e5x and split vaccine was associated with the proliferation of CD4(+) T cells. Our results suggest that a strategy of co-immunization with seasonal split and M2e5x protein vaccines could be a promising approach for overcoming the limitation of strain-specific protection by current influenza vaccination.
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Yu-Na
authors.initials: YN
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Animal and Plant Quarantine Agency, 175 Anyangro, Anyang, Gyeonggi-do 430-757, Republic of Korea.
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kim
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggi-do, Republic of Korea.
authors.forename: Jongsang
authors.initials: J
authors.lastname: Lee
authors.affiliation: BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggi-do, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Kim
authors.affiliation: Mogam Biotechnology Research Institute, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Suk-Hoon
authors.initials: SH
authors.lastname: Ha
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address: skang24@gsu.edu.
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D056738:Cross Protection; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D007106:Immune Sera; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D007371:Interferon-gamma; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: AS04; Influenza virus; M2e5x; Protein; Split vaccine