Synthetic peptides containing B- and T-cell epitope of dengue virus-2 E domain III provoked B- and T-cell responses

被引:40
|
作者
Li, Shanfeng [1 ]
Peng, Liang [1 ]
Zhao, Wei [1 ]
Zhong, Hua [1 ]
Zhang, Fuchun [2 ]
Yan, Ziqiang [3 ]
Cao, Hong [1 ]
机构
[1] So Med Univ, Dept Microbiol, Sch Publ Hlth & Trop Med, Guangzhou 510515, Guangdong, Peoples R China
[2] Guangzhou 8th Peoples Hosp, Guangzhou 510060, Guangdong, Peoples R China
[3] Guangzhou Ctr Dis Control Prevent, Guangzhou 510080, Guangdong, Peoples R China
关键词
Dengue; Multi-epitope peptide; Domain III; Vaccine; PHASE-I TRIAL; NEUTRALIZING ANTIBODIES; ENVELOPE PROTEIN; VACCINE DESIGN; PROTECTIVE ANTIBODIES; SEROTYPES; MICE; RECOMBINANT; INDUCTION; PATHOGENESIS;
D O I
10.1016/j.vaccine.2011.03.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Our previous work applied a combination of bioinformatics approaches and in vitro assays to identify the dengue-2 virus (DENV-2)-specific B- and T-cell epitopes. In this report, we first evaluated the antigenicity of both B- and T-cell epitopes reacting with different sera against DENV-2 by ELISA as well as the ability of T-cell epitope to activate CD4(+) T-cell producing IFN-gamma using ELISPOT, which showed a specific reactivity between either B- or T-cell epitope and DENV-2 antisera, and a significant increase of IFN-gamma producing cells in DENV-2 infected mice. Then, a multi-epitope peptide containing the above B-, T-cell epitopes of envelope domain III (EDIII) of DENV-2 and pan-DR epitope (PADRE) was bioinformatically designed and synthesized. The verification of its immunogenicity and protective effect was performed in in vitro and in vivo experiments. The results showed that a high level of antibody in mice elicited by the multi-epitope peptide was detected by ELISA and the anti-peptide sera binding to the vero cells infected with DEN-2 was observed with immunofluorescence test. More importantly, the peptide could induce lymphoproliferation in vitro and a predominant Th1 type of immune response was examined by flow cytometry. We also found that the virus replication in the mice vaccinated with the multi-epitope peptide was obviously less than that of the control groups. These results may provide some important information for the development of dengue vaccine. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3695 / 3702
页数:8
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