期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 204, 期 12, 页码 2789-2796出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20070607
关键词
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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.
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