A fusion DNA vaccine that targets antigen-presenting cells increases protection from viral challenge

被引:84
作者
Deliyannis, G
Boyle, JS
Brady, JL
Brown, LE
Lew, AM [1 ]
机构
[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
[2] Univ Melbourne, Dept Microbiol & Immunol, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3052, Australia
[3] CSL Ltd, Parkville, Vic 3052, Australia
关键词
D O I
10.1073/pnas.120162497
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Improving the immunological potency, particularly the Ab response, is a serious hurdle for the protective efficacy and hence broad application of DNA vaccines. We examined the immunogenicity and protective efficacy of a hemagglutinin-based influenza DNA vaccine that was targeted to antigen-presenting cells (APCs) by fusion to CTLA4, The targeted vaccine was shown to induce an accelerated and increased Ab response (as compared with those receiving the nontargeted control) that was predominated by IgG1 and recognized conformationally dependent viral epitopes, Moreover, mice receiving the APC-targeted DNA vaccine had significantly reduced viral titers (100-fold) after a nonlethal virus challenge. The increased protective efficacy was most likely because of increased Ab responses, as cytotoxic T lymphocyte responses were not enhanced. Targeting was demonstrated by direct binding studies of CTLA4 fusion proteins to the cognate ligand (B7; expressed on APCs in vivo). In addition, a targeted protein was detected at 4-fold higher levels in draining lymph nodes within 2-24 h of administration. Therefore, this study demonstrates that targeting DNA-encoded antigen to APCs results in enhanced immunity and strongly suggests that this approach may be useful in improving the protective efficacy of DNA vaccines.
引用
收藏
页码:6676 / 6680
页数:5
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