Mucosal vaccination using claudin-4-targeting

Biomaterials. 2010 Jul;31(20):5463-71. doi: 10.1016/j.biomaterials.2010.03.047.


Mucosa-associated lymphoid tissue (MALT) plays pivotal roles in mucosal immune responses. Efficient delivery of antigens to MALT is a critical issue for the development of mucosal vaccines. Although claudin-4 is preferentially expressed in MALT in the gut, a claudin-4-targeting approach for mucosal vaccination has never been developed. In the present study, we found that claudin-4 is expressed in nasal MALT, and we prepared a fusion protein of ovalbumin (OVA) as a model antigen with a claudin-4-binder, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) (OVA-C-CPE). Nasal immunization with OVA-C-CPE, but not a mixture of OVA and C-CPE, induced the production of OVA-specific serum IgG and nasal, vaginal and fecal IgA. Deletion of the claudin-4-binding region in OVA-C-CPE attenuated the induction of the immune responses. OVA-C-CPE immunization activated both Th1 and Th2 responses, and nasal immunization with OVA-C-CPE showed anti-tumor activity in mice inoculated with OVA-expressing thymoma cells. These results indicate that the claudin-4-targeting may be a potent strategy for nasal vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Claudin-4
  • Enterotoxins / chemistry
  • Enterotoxins / immunology
  • Female
  • Gene Expression Regulation
  • Immunity, Humoral / immunology
  • Immunity, Mucosal / immunology*
  • Lymphoid Tissue / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nasal Mucosa / immunology*
  • Nasopharynx / metabolism
  • Ovalbumin / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Thymoma / immunology
  • Vaccination*


  • Cancer Vaccines
  • Claudin-4
  • Cldn4 protein, mouse
  • Enterotoxins
  • Membrane Proteins
  • enterotoxin, Clostridium
  • Ovalbumin