2003 Fiscal Year Final Research Report Summary
Development of novel vaccine adjuvant for infectious disease
| Project/Area Number |
13557204
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
MAYUMI Tadanori Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (00098485)
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| Co-Investigator(Kenkyū-buntansha) |
TSUTSUMI Yasuo Osaka University, Graduate School of Pharmaceutical Sciences, Research Associate, 薬学研究科, 助手 (50263306)
NAKAGAWA Shinsaku Osaka University, Graduate School of Pharmaceutical Sciences, associate Professor, 薬学研究科, 助教授 (70207728)
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| Project Period (FY) |
2001 – 2003
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| Keywords | vaccine / mucosal immunity / fusogenic liposomes / antibody production / MHC class I / MHC class II / M cell / cytotoxic T lymphocyte |
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| Research Abstract |
We prepared fusogenic liposomes by fusing conventional liposomes with an ultra-violet inactivated Sendai virus. Fusogenic liposomes can deliver encapsulated contents into the cytoplasm directly in a Sendai virus fusion-dependent manner. Based on the high delivery rates into the cytoplasm, we examined the use of fusogenic liposomes as an antigen delivery vehicle. Nasal administration of antigens using fusogenic liposome efficiently delivered antigens to antigen-sampling M cells in nasopharyngeal-associated lymphoreticular tissue. Additionally, fusogenic liposomes also effectively delivered the antigens into epithelial cells and macrophages in nasopharyngeal-associated lymphoreticular tissue and nasal passages. In vitro Antigen presentation assays clearly showed that fusogenic liposomes effectively presented encapsulated antigens via the MHC class II-dependent pathway of epithelial cells as well as macrophages. Fusogenic liposomes also have an adjuvant activity against mucosal epithelial cells to enhance MHC class II expression. According to these high delivery and adjuvant activities of fusogenic liposomes, nasal immunization with OVA-encapsulated fusogenic liposomes induced high levels of OVA-specific CD4(+) Th1 and Th2 cell responses. Furthermore, Antigen-specific CTL responses and antibody productions were also elicited at both mucosal and systemic sites by nasal immunization with antigen-encapsulated fusogenic liposomes. These results indicate that fusogenic liposome is a versatile and effective system for the stimulation of antigen-specific immune responses at both mucosal and systemic compartments.
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