Enhanced effects of DNA vaccine against botulinum neurotoxin serotype A by targeting antigen to dendritic cells

被引:8
作者
Chen, Bo-Yang [1 ]
Zhou, Guo [1 ]
Li, Qing-Li [1 ,2 ]
Lu, Jian-Sheng [1 ]
Shi, Dan-Yang [1 ]
Pang, Xiao-Bin [2 ]
Zhou, Xiao-Wei [1 ]
Yu, Yun-Zhou [1 ]
Huang, Pei-Tang [1 ]
机构
[1] Beijing Inst Biotechnol, 20 Dongdajie St, Beijing 100071, Peoples R China
[2] Henan Univ, Pharmaceut Coll, Kaifeng 475001, Peoples R China
关键词
Dendritic cells; Botulinum neurotoxin; DEC205; DNA vaccine; IN-VIVO; CLOSTRIDIUM-BOTULINUM; IMMUNE-RESPONSES; REPLICON VACCINE; HC SUBUNIT; IMMUNOGENICITY; EXPRESSION; PROTEIN; DOMAIN; RECRUITMENT;
D O I
10.1016/j.imlet.2017.08.004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
As dendritic cells (DCs) play a critical role in priming antigen-specific immune responses, the efficacy of DNA vaccines may be enhanced by targeting the encoded antigen proteins to DCs. In this study, we constructed a DC targeted DNA vaccine encoding the He domain of botulinum neurotoxin serotype A (AHc) fused with scDEC, a single-chain Fv antibody (scFv) specific for the DC-restricted antigen-uptake receptor DEC205. Intramuscular injections of mice with the DC-targeted DNA vaccine (pVAX1-scDEC-AHc) stimulated more DCs to mature than the non-targeted DNA vaccine (pVAX1-SAHc) in the splenocytes. The DC-targeted DNA vaccine could induce more DCs maturation at the site of inoculation. The DC-targeted DNA vaccine induced stronger AHc-specific humoral immune responses, lymphocyte proliferative responses and protective potency against BoNT/A in mice than did pVAX1-SAHc. Moreover, the DC-targeting DNA vaccine provided effective protection after only two inoculations. In summary, these results showed that the DC-targeted fusion DNA vaccine could generate strong immunity, indicating that maturation of DCs induced by pVAX1-scDEC-AHc may be helpful for priming and boosting immune responses. Thus, we propose that the strategy of targeting antigen to DCs in vivo via DEC205 can enhance effectively the potency of DNA vaccines against BoNTs or other pathogens in an animal model.
引用
收藏
页码:118 / 124
页数:7
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