title: A novel M cell-specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses.
abstract: Mucosally ingested and inhaled antigens are taken up by membranous or microfold cells (M cells) in the follicle-associated epithelium of Peyer's patches or nasopharynx-associated lymphoid tissue. We established a novel M cell-specific monoclonal antibody (mAb NKM 16-2-4) as a carrier for M cell-targeted mucosal vaccine. mAb NKM 16-2-4 also reacted with the recently discovered villous M cells, but not with epithelial cells or goblet cells. Oral administration of tetanus toxoid (TT)- or botulinum toxoid (BT)-conjugated NKM 16-2-4, together with the mucosal adjuvant cholera toxin, induced high-level, antigen-specific serum immunoglobulin (Ig) G and mucosal IgA responses. In addition, an oral vaccine formulation of BT-conjugated NKM 16-2-4 induced protective immunity against lethal challenge with botulinum toxin. An epitope analysis of NKM 16-2-4 revealed specificity to an alpha(1,2)-fucose-containing carbohydrate moiety, and reactivity was enhanced under sialic acid-lacking conditions. This suggests that NKM 16-2-4 distinguishes alpha(1,2)-fucosylated M cells from goblet cells containing abundant sialic acids neighboring the alpha(1,2) fucose moiety and from non-alpha(1,2)-fucosylated epithelial cells. The use of NKM 16-2-4 to target vaccine antigens to the M cell-specific carbohydrate moiety is a new strategy for developing highly effective mucosal vaccines.
authors.affiliation: Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yuki
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumura
authors.forename: Mio
authors.initials: M
authors.lastname: Mejima
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Terahara
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Iwatsuki-Horimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kohda
authors.forename: Shunji
authors.initials: S
authors.lastname: Kozaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Igarashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology*; D020397:Goblet Cells / Q000276:immunology; D037102:Lectins / Q000276:immunology; D051379:Mice; D010581:Peyer's Patches / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000276:immunology*; D014612:Vaccines / Q000276:immunology* / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D037102:Lectins; D014612:Vaccines