https://scholars.lib.ntu.edu.tw/handle/123456789/458687
標題: | Enhancement of sindbis virus self-replicating RNA vaccine potency by linkage of Mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene | 作者: | WEN-FANG CHENG Hung C.-F. Chai C.-Y. Hsu K.-F. He L. Rice C.M. Ling M. Wu T.-C. |
公開日期: | 2001 | 卷: | 166 | 期: | 10 | 起(迄)頁: | 6218-6226 | 來源出版物: | Journal of Immunology | 摘要: | Recently, self-replicating RNA vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid vaccine development. Unlike naked DNA vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 E7 as a model Ag to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results indicated that this RNA replicon vaccine containing an E7/HSP70 fusion gene generated significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did vaccines containing the wild-type E7 gene. Furthermore, our in vitro studies demonstrated that E7 Ag from E7/HSP70 RNA replicon-transfected cells can be processed by bone marrow-derived dendritic cells and presented more efficiently through the MHC class I pathway than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7 converted a less effective vaccine into one with significant potency against E7-expressing tumors. This antitumor effect was dependent on NK cells and CD8+ T cells. These results indicated that fusion of HSP70 to an Ag gene may greatly enhance the potency of self-replicating RNA vaccines. |
URI: | 2-s2.0-0035873726 https://scholars.lib.ntu.edu.tw/handle/123456789/458687 |
ISSN: | 0022-1767 | DOI: | 10.4049/jimmunol.166.10.6218 | SDG/關鍵字: | CD8 antigen; gene product; heat shock protein 70; major histocompatibility antigen class 1; nucleic acid; RNA replicon vaccine; unclassified drug; virus vaccine; virus vector; animal cell; animal experiment; animal model; antineoplastic activity; apoptosis; article; cellular immunity; controlled study; drug potency; female; fusion gene; genetic transfection; immunity; mouse; Mycobacterium tuberculosis; natural killer cell; nonhuman; priority journal; RNA virus; Sindbis virus; vaccination; virus replication; Wart virus |
顯示於: | 醫學系 |
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