A novel M cell-specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses

Tomonori Nochi, Yoshikazu Yuki, Akiko Matsumura, Mio Mejima, Kazutaka Terahara, Dong Young Kim, Satoshi Fukuyama, Kiyoko Iwatsuki-Horimoto, Yoshihiro Kawaoka, Tomoko Kohda, Shunji Kozaki, Osamu Igarashi, Hiroshi Kiyono

Research output: Contribution to journalArticlepeer-review

150 Citations (Scopus)

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 α(1,2)-fucose-containing carbohydrate moiety, and reactivity was enhanced under sialic acid-lacking conditions. This suggests that NKM 16-2-4 distinguishes α(1,2)-fucosylated M cells from goblet cells containing abundant sialic acids neighboring the α(1,2) fucose moiety and from non-α(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. JEM

Original languageEnglish
Pages (from-to)2789-2796
Number of pages8
JournalJournal of Experimental Medicine
Volume204
Issue number12
DOIs
Publication statusPublished - 2007 Nov 26
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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