title: Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1.
abstract: Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that crossreacted with human and avian M2 sequences and produced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A.
authors.affiliation: Food and Drug Administration, Bethesda, Maryland, USA. tompkins@vet.uga.edu
authors.forename: Stephen Mark
authors.initials: SM
authors.lastname: Tompkins
authors.forename: Zi-Shan
authors.initials: ZS
authors.lastname: Zhao
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lo
authors.forename: Julia A
authors.initials: JA
authors.lastname: Misplon
authors.forename: Teresa
authors.initials: T
authors.lastname: Liu
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Ye
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hogan
authors.forename: Zhengqi
authors.initials: Z
authors.lastname: Wu
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Benton
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Epstein
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D005260:Female; D005814:Genes, Viral; D005822:Genetic Vectors / Q000008:administration & dosage / Q000378:metabolism; D007115:Immunization Schedule; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007473:Ion Channels / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D007473:Ion Channels; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins