Journal
BIOMATERIALS
Volume 31, Issue 20, Pages 5463-5471Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.03.047
Keywords
Immunomodulation; Mucosa; Drug delivery; Epithelium
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan [21689006]
- Ministry of Health, Labor and Welfare of Japan
- Takeda Science Foundation
- Suzuken Memorial Foundation
- Kansai Biomedical Cluster project in Saito
- Japan Science and Technology Agency
- Japan Health Sciences Foundation
- Japan Society for the Promotion of Science for Young Scientists
- Grants-in-Aid for Scientific Research [21689006] Funding Source: KAKEN
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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. (C) 2010 Elsevier Ltd. All rights reserved.
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