碩士 / 國立成功大學 / 微生物及免疫學研究所 / 98 / Patients infected by dengue viruses (DV) may display dengue fever, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Hemorrhagic syndromes of DHF/DSS include thrombocytopenia, coagulopathy and vasculopathy, which are related with dysfunction of endothelial cells and platelets. Previous studies in our laboratory showed that antibodies (Abs) against DV nonstructural protein 1 (NS1) cross-react with human endothelial cells and induce apoptosis. Platelet dysfunction and bleeding tendency are also induced by anti-DV NS1 Abs. Using sequence homology analysis, we found that the C-terminal region of DV NS1 protein contains cross-reactive epitopes shared with self-antigens. For safety in vaccine development, the cross-reactive epitopes of DV NS1 protein should be deleted or modified. We have generated the chimeric NS1 protein, which consists of N-terminal DV NS1 (a.a. 1-270) and C-terminal JEV NS1 (a.a. 271-352) (designated DJ NS1). The anti-DJ NS1 Abs showed lower binding activity to human endothelial cells and platelets than that of anti-DV NS1 Abs. In the murine model, DV NS1 immunization caused prolonged bleeding time, but DJ NS1 immunization did not. Passive immunization with anti-DV NS1 or anti-DJ NS1 Abs could reduce DV-induced prolonged bleeding time and hemorrhage on the local skin. KU812 basophil/mast cell line was susceptible to DV infection without enhancing Abs. Anti-DJ NS1 Abs induced DV-infected KU812 cells to undergo apoptosis. Moreover, the expression of MIP-1 alpha and MIP-1 beta in DV-infected KU812 cells was also reduced by anti-DJ NS1 Abs. According to these findings, DJ NS1 may provide a strategy for dengue vaccine development.
| Identifer | oai:union.ndltd.org:TW/098NCKU0380008 |
| Date | January 2010 |
| Creators | Chia-HuiHuang, 黃佳慧 |
| Contributors | Yee-Shin Lin, 林以行 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | en_US |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 65 |
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