title: Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection.
abstract: A broadly cross-protective influenza vaccine that can be administrated by a painless self-immunization method would be a value as a potential universal mass vaccination strategy. This study developed a minimally-invasive microneedle (MN) patch for skin vaccination with virus-like particles containing influenza virus heterologous M2 extracellular (M2e) domains (M2e5x VLPs) as a universal vaccine candidate without adjuvants. The stability of M2e5x VLP-coated microneedles was maintained for 8weeks at room temperature without losing M2e antigenicity and immunogenicity. MN skin immunization induced strong humoral and mucosal M2e antibody responses and conferred cross-protection against heterosubtypic H1N1, H3N2, and H5N1 influenza virus challenges. In addition, M2e5x VLP MN skin vaccination induced T-helper type 1 responses such as IgG2a isotype antibodies and IFN-γ producing cells at higher levels than those by conventional intramuscular injection. These potential immunological and logistic advantages for skin delivery of M2e5x VLP MN vaccines could offer a promising approach to develop an easy-to-administer universal influenza vaccine.
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, Gyeonggido 430-757, South Korea.
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kim
authors.affiliation: School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Chemical and Materials Engineering, University of Alberta, AB T6G 2M9, Canada.
authors.forename: Hyo-Jick
authors.initials: HJ
authors.lastname: Choi
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.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggido, South Korea.
authors.forename: Jongsang
authors.initials: J
authors.lastname: Lee
authors.affiliation: BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggido, South Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Kim
authors.affiliation: National Institute of Biological Resources, Incheon 404-708, South Korea.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Chemical and Materials Engineering, University of Alberta, AB T6G 2M9, Canada.
authors.forename: Carlo
authors.initials: C
authors.lastname: Montemagno
authors.affiliation: School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
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: D000279:Administration, Cutaneous; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D056738:Cross Protection; D016503:Drug Delivery Systems; D005260:Female; D007074:Immunoglobulin G / 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*; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008807:Mice, Inbred BALB C; D008845:Microinjections; D009339:Needles; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015850:Interleukin-6; D058425:Vaccines, Virus-Like Particle; D014764:Viral Proteins; C577686:interleukin-6, mouse; D007371:Interferon-gamma
keywords: Cross-protection; Influenza universal vaccine; M2e5x VLPs; Microneedles