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

Cited 121 time in Web of Science Cited 144 time in Scopus
Authors
Nochi, Tomonori; Yuki, Yoshikazu; Matsumura, Akiko; Mejima, Mio; Terahara, Kazutaka; Kim, Dong-Young; Fukuyama, Satoshi; Iwatsuki-Horimoto, Kiyoko; Kawaoka, Yoshihiro; Kohda, Tomoko; Kozaki, Shunji; Igarashi, Osamu; Kiyono, Hiroshi
Issue Date
2007
Publisher
Rockefeller University Press
Citation
J. Exp. Med. 204:2789-2796
Keywords
Antibodies, Monoclonal/*immunology/pharmacokineticsAntibody SpecificityAntigens/*immunologyGoblet Cells/immunologyLectins/immunologyPeyer's Patches/immunologyRatsRats, Sprague-DawleyRespiratory Mucosa/*immunologyVaccines/*immunology/pharmacokinetics
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.
ISSN
1540-9538 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17984304

http://hdl.handle.net/10371/11171
DOI
https://doi.org/10.1084/jem.20070607
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College of Medicine/School of Medicine (의과대학/대학원)Otorhinolaryngology (이비인후과학전공)Journal Papers (저널논문_이비인후과학전공)
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