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

J Exp Med 204; 2789-2796, 2007
Tomonori Nochi1,2)、Yoshikazu Yuki1,2)、Akiko Matsumura1,2)、Mio Mejima1,2)、Kazutaka Terahara1,2)、Dong-Young Kim1,2)、Satoshi Fukuyama1,2)、Kiyoko Iwatsuki-Horimoto2,3)、Yoshihiro Kawaoka2,3)、Tomoko Kohda4)、Shunji Kozaki4)、Osamu Igarashi1,2)、Hiroshi Kiyono1,2)
1: Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo
2: Division of Virology, The Institute of Medical Science, The University of Tokyo
3: Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation
4: Laboratory of Veterinary Epidemiology, Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University

Since the mucosal immune system induces antigen-specific immune responses in both systemic and mucosal compartments, mucosal vaccine is considered to be an ideal strategy for inducing effective immunity against mucosal infectious diseases. In spite of its advantage, no oral vaccines except polio vaccine are now available in human, because of several obstacles, which need to be overcome.
M cells located in the follicle-associated epithelium (FAE) of Peyer's patches (PPs) or nasopharynx-associated lymphoid tissue (NALT) in aero-digestive tract take up ingested or inhaled luminal antigens for the initiation of antigen-specific immune response. We here established a novel monoclonal antibody (mAb NKM 16-2-4), specific for M cells in PPs and NALT, as a carrier of M-cell–targeted mucosal vaccine. It also reacted with the recently discovered villous M cells but not with epithelial cells or goblet cells. Oral administration of low doses of tetanus toxoid (TT)- or botulinum toxoid (BT)-conjugated NKM 16-2-4 together with mucosal adjuvant cholera toxin (CT) resulted in the induction of high-levels of antigen-specific serum IgG and mucosal IgA responses; TT- or BT-conjugated control rat IgG induced no- or very low-level antigen-specific immune responses. In addition, oral vaccine with BT-conjugated NKM 16-2-4 induced protective immunity against 10000x LD50 dose of botulinum toxin challenge. Epitope analysis of NKM 16-2-4 revealed specificity to an α(1,2)-fucose–containing carbohydrate moiety in M cells. These results show that M cell-specific carbohydrate-targeted mucosal vaccine with NKM 16-2-4 is a new strategy for developing highly effective mucosal vaccines.