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杆状病毒展示的肠道病毒 71 病毒衣壳蛋白 VP1 作为一种 II 型跨膜蛋白,可在免疫小鼠中引发保护性 B 和 T 细胞应答。

Display of enterovirus 71 VP1 on baculovirus as a type II transmembrane protein elicits protective B and T cell responses in immunized mice.

机构信息

Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Republic of Singapore.

出版信息

Virus Res. 2012 Sep;168(1-2):64-72. doi: 10.1016/j.virusres.2012.06.014. Epub 2012 Jun 20.

Abstract

Human enterovirus 71 (EV71) has become a major public health threat across Asia Pacific. The virus causes hand, foot, and mouth disease which can lead to neurological complications in young children. There are no specific antivirals or vaccines against EV71 infection. The major neutralizing epitope of EV71 is located in the carboxy-terminal half of the VP1 protein at amino acid positions 215-219 (Lim et al., 2012). To study the immunogenicity of VP1 we have developed a baculovirus vector which displays VP1 as a type II transmembrane protein, providing an accessible C-terminus. Immunization of mice with this recombinant baculovirus elicited neutralizing antibodies against heterologous EV71 in an in vitro microneutralization assay. Passive protection of neonatal mice confirmed the prophylactic efficacy of the antisera. Additionally, EV71 specific T cell responses were stimulated. Taken together, our results demonstrate that the display of VP1 as a type II transmembrane protein efficiently stimulated both humoral and cellular immunities.

摘要

人肠道病毒 71 型(EV71)已成为亚太地区主要的公共卫生威胁。该病毒会引起手足口病,可导致幼儿出现神经并发症。目前尚无针对 EV71 感染的特效抗病毒药物或疫苗。EV71 的主要中和表位位于 VP1 蛋白羧基端的一半,位于氨基酸位置 215-219(Lim 等人,2012)。为了研究 VP1 的免疫原性,我们开发了一种杆状病毒载体,该载体将 VP1 作为 II 型跨膜蛋白展示,提供了可及的 C 端。用这种重组杆状病毒免疫小鼠可在体外微量中和试验中诱导针对异源 EV71 的中和抗体。新生小鼠的被动保护证实了抗血清的预防功效。此外,还刺激了 EV71 特异性 T 细胞反应。综上所述,我们的结果表明,将 VP1 作为 II 型跨膜蛋白展示可有效刺激体液和细胞免疫。

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