title: Supplementation of influenza split vaccines with conserved M2 ectodomains overcomes strain specificity and provides long-term cross protection.
abstract: Current influenza vaccines do not provide good protection against antigenically different influenza A viruses. As an approach to overcome strain specificity of protection, this study demonstrates significantly improved long-term cross protection by supplementing split vaccines with a conserved molecular target, a repeat of the influenza M2 ectodomain (M2e) expressed on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Intramuscular immunization with H1N1 split vaccine (A/California/07/2009) supplemented with M2e5x VLPs induced M2e-specific humoral and cellular immune responses, and shaped the host responses to the vaccine in the direction of T-helper type 1 responses inducing dominant IgG2a isotype antibodies as well as interferon-γ (IFN-γ) producing cells in systemic and mucosal sites. Upon lethal challenge, M2e5x VLP-supplemented vaccination lowered lung viral loads and induced long-term cross protection against H3N2 or H5N1 subtype influenza viruses over 12 months. M2e antibodies, CD4 T cells, and CD8 T cells were found to contribute to improving heterosubtypic cross protection. In addition, improved cross protection by supplemented vaccination with M2e5x VLPs was mediated via Fc receptors. The results support evidence that supplementation with M2e5x VLPs is 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, Georgia, USA; Animal and Plant Quarantine Agency, Anyang City, Gyeonggi-do, 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, Georgia, 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, Georgia, USA.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Ko
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Kwon
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: Department of Global medical Science, Sungshin Women's University, Seoul, Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Song
authors.affiliation: Animal and Plant Quarantine Agency, Anyang City, Gyeonggi-do, Korea.
authors.forename: Byung-Min
authors.initials: BM
authors.lastname: Song
authors.affiliation: Animal and Plant Quarantine Agency, Anyang City, Gyeonggi-do, Korea.
authors.forename: Youn-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Animal and Plant Quarantine Agency, Anyang City, Gyeonggi-do, Korea.
authors.forename: Jun-Gu
authors.initials: JG
authors.lastname: Choi
authors.affiliation: Animal and Plant Quarantine Agency, Anyang City, Gyeonggi-do, Korea.
authors.forename: Hyun-Mi
authors.initials: HM
authors.lastname: Kang
authors.affiliation: Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Fu-Shi
authors.initials: FS
authors.lastname: Quan
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA. Electronic address: skang24@gsu.edu.
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000818:Animals; D056738:Cross Protection / Q000276:immunology*; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control
chemical_list: D007252:Influenza Vaccines