Recombinant lipidated dengue-4 envelope protein domain III elicits protective immunity

被引:29
作者
Chiang, Chen-Yi [1 ]
Hsieh, Chun-Hsiang [1 ]
Chen, Mei-Yu [1 ]
Tsai, Jy-Ping [1 ]
Liu, Hsueh-Hung [1 ]
Liu, Shih-Jen [1 ,2 ]
Chong, Pele [1 ,2 ]
Leng, Chih-Hsiang [1 ,2 ]
Chen, Hsin-Wei [1 ,2 ]
机构
[1] Natl Hlth Res Inst, Natl Inst Infect Dis & Vaccinol, Zhunan 350, Miaoli, Taiwan
[2] China Med Univ, Grad Inst Immunol, Taichung, Taiwan
关键词
Dengue virus; Envelope protein domain III; Lipoprotein; Vaccine; NONHUMAN-PRIMATES; NEUTRALIZING ANTIBODIES; FUSION PROTEIN; VIRUS; VACCINE; MICE; IMMUNOGENICITY; RESPONSES; CELLS; GLYCOPROTEIN;
D O I
10.1016/j.vaccine.2014.01.041
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The combination of recombinant protein antigens with an immunostimulator has the potential to greatly increase the immunogenicity of recombinant protein antigens. In the present study, we selected the dengue-4 envelope protein domain III as a dengue vaccine candidate and expressed the protein in lipidated form using an Escherichia coli-based system. The recombinant lipidated dengue-4 envelope protein domain III folded into the proper conformation and competed with the dengue-4 virus for cellular binding sites. Mice immunized with lipidated dengue-4 envelope protein domain III without exogenous adjuvant had higher frequencies of dengue-4 envelope protein domain III-specific B cells secreting antibodies than mice immunized with the nonlipidated form. Importantly, lipidated dengue-4 envelope protein domain III-immunized mice demonstrated a durable neutralizing antibody response and had reduced viremia levels after challenge. The study demonstrates that lipidated dengue-4 envelope protein domain III is immunogenic and may be a potential dengue vaccine candidate. Furthermore, the lipidation strategy can be applied to other serotypes of dengue virus. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1346 / 1353
页数:8
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