title: Cross Protection against Influenza A Virus by Yeast-Expressed Heterologous Tandem Repeat M2 Extracellular Proteins.
abstract: The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04-adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, M2e5x immune sera were found to confer protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. Also, M2e5x-immune complexes of virus-infected cells stimulated macrophages to secrete cytokines via Fc receptors, indicating a possible mechanism of protection. The present study provides evidence that M2e5x proteins produced in yeast cells could be developed as a potential universal influenza vaccine.
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, United States of America.
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 30303, United States of America; Animal and Plant Quarantine Agency, Anyang, Gyeonggi-do, South 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 30303, United States of America.
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, Georgia 30303, United States of America.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggi-do, South Korea.
authors.forename: Jongsang
authors.initials: J
authors.lastname: Lee
authors.affiliation: BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggi-do, South Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Kim
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, United States of America.
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002642:Chick Embryo; D003429:Cross Reactions; D004285:Dogs; D005260:Female; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity*; D007252:Influenza Vaccines / Q000276:immunology* / Q000494:pharmacology; D061985:Madin Darby Canine Kidney Cells / Q000821:virology; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D010843:Pichia / Q000235:genetics; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020080:Tandem Repeat Sequences; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D007252:Influenza Vaccines; D011961:Receptors, Fc; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins