title: A novel mucosal vaccine targeting Peyer's patch M cells induces protective antigen-specific IgA responses.
abstract: Mucosal vaccines can induce mucosal immunity, including antigen-specific secretory IgA production, to protect from invasion by pathogens and to neutralize toxins at mucosal surfaces. We established an effective antigen-delivering fusion protein, anti-GP2-SA, as a mucosal vaccine. The anti-GP2-SA consists of streptavidin (SA) fused to the antigen-binding fragment region from a mAb against glycoprotein 2 (GP2), an antigen-uptake receptor specifically expressed on M cells. Anti-GP2-SA targets antigen-sampling M cells in the follicle-associated epithelium covering Peyer's patches. Immunofluorescence showed that anti-GP2-SA specifically bound to M cells. Orally administered biotinylated ovalbumin peptide (bOVA) conjugated with anti-GP2-SA more efficiently induced OVA-specific fecal IgA secretion compared with bOVA alone or bOVA conjugated with SA. Furthermore, mice immunized by oral administration of the biotinylated Salmonella enterica serovar Typhimurium (S. Typhimurium) lysate conjugated with anti-GP2-SA were significantly better protected from subsequent infection by virulent S. Typhimurium than mice treated with the bacterial lysate alone or conjugated with SA. These results suggest that anti-GP2-SA-based M-cell-targeting vaccines are a novel strategy for inducing efficient mucosal immunity.
authors.affiliation: Division of Immunobiology, Graduate School of Supramolecular Biology, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shima
authors.affiliation: Laboratory for Immunogenomics, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan Gut Environmental Systems Biology, Integrated Omics, Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0035, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, Kanagawa, 229-8558, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Fukuoka
authors.affiliation: Laboratory for Immunogenomics, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Division of Immunobiology, Graduate School of Supramolecular Biology, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan ohno@rcai.riken.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology*; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology*; D010581:Peyer's Patches / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012480:Salmonella Infections / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000941:Antigens; D000942:Antigens, Bacterial; D058851:GPI-Linked Proteins; C495998:Gp2 protein, mouse; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D011993:Recombinant Fusion Proteins; D014612:Vaccines
keywords: IgA; M cell; mucosal vaccine; vaccine delivery