title: Virus-like particles containing multiple M2 extracellular domains confer improved cross-protection against various subtypes of influenza virus.
abstract: The extracellular domain of M2 (M2e), a small ion channel membrane protein, is well conserved among different human influenza A virus strains. To improve the protective efficacy of M2e vaccines, we genetically engineered a tandem repeat of M2e epitope sequences (M2e5x) of human, swine, and avian origin influenza A viruses, which was expressed in a membrane-anchored form and incorporated in virus-like particles (VLPs). The M2e5x protein with the transmembrane domain of hemagglutinin (HA) was effectively incorporated into VLPs at a several 100-fold higher level than that on influenza virions. Intramuscular immunization with M2e5x VLP vaccines was highly effective in inducing M2e-specific antibodies reactive to different influenza viruses, mucosal and systemic immune responses, and cross-protection regardless of influenza virus subtypes in the absence of adjuvant. Importantly, immune sera were found to be sufficient for conferring protection in naive mice, which was long-lived and cross-protective. Thus, molecular designing and presenting M2e immunogens on VLPs provide a promising platform for developing universal influenza vaccines without using adjuvants.
authors.affiliation: Center for Inflammation, Immunity & Infection, and Department of Biology, Georgia State University, Atlanta, Georgia 30322, USA.
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kim
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Song
authors.forename: Eunju
authors.initials: E
authors.lastname: O
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Kwon
authors.forename: Youn-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D056738:Cross Protection; D003429:Cross Reactions; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology* / Q000494:pharmacology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D030781:Organisms, Genetically Modified; D018411:Spodoptera / Q000235:genetics; D020080:Tandem Repeat Sequences; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000276:immunology; D014771:Virion / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007106:Immune Sera; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins