Recombinant lipidated dengue-4 envelope protein domain III elicits protective immunity
Recombinant lipidated dengue-4 envelope protein domain III elicits protective immunity
复制标题
DOI：
10.1016/j.vaccine.2014.01.041
复制
发表时间：
2014-03-10
期刊：
影响因子：
5.5
通讯作者：
Chen, Hsin-Wei
中科院分区：
文献类型：
--
作者：
Chiang, Chen-Yi;Hsieh, Chun-Hsiang;Chen, Hsin-Wei
重组蛋白抗原与免疫刺激剂的结合有可能大大提高重组蛋白抗原的免疫原性。在本研究中，我们选择登革热-4包膜蛋白结构域III作为登革热候选疫苗，并使用基于大肠杆菌的系统以脂化形式表达该蛋白。重组脂化的登革-4包膜蛋白结构域III折叠成合适的构象，并与登革-4病毒竞争细胞结合位点。无外源佐剂的脂化登革热-4包膜蛋白结构域III免疫小鼠比非脂化形式免疫小鼠具有更高的登革热-4包膜蛋白结构域III特异性B细胞分泌抗体的频率。重要的是，脂化的登革热-4包膜蛋白结构域iii免疫小鼠表现出持久的中和抗体反应，并在攻击后降低了病毒血症水平。研究表明，脂化的登革热-4包膜蛋白结构域III具有免疫原性，可能是一种潜在的登革热候选疫苗。此外，脂化策略可应用于其他血清型登革热病毒。(C) 2014年作者。Elsevier Ltd.出版。版权所有。
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.