Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design.
Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design.
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DOI：
10.1038/s41541-020-00269-1
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发表时间：
2021-01-08
期刊：
影响因子：
9.2
通讯作者：
Patel AH
中科院分区：
文献类型：
--
作者：
Cowton VM;Owsianka AM;Fadda V;Ortega-Prieto AM;Cole SJ;Potter JA;Skelton JK;Jeffrey N;Di Lorenzo C;Dorner M;Taylor GL;Patel AH
HCV疫苗的开发受到病毒高度遗传多样性和包膜糖蛋白变异性的阻碍。克服这一问题的一个策略是确定保守的、功能上重要的区域，如广泛中和抗体（bNAb）的表位，并将其用作基于结构的疫苗设计的基础。在这里，我们报告了一个抗独特型的方法，产生了一个抗体，模仿高度保守的中和表位上的HCV E2。至关重要的是，使用诱变筛选来鉴定命名为B2.1A的抗体，其与bNAb AP 33的结合特征与原始抗原的结合特征非常相似。蛋白质晶体学证实B2.1 A是AP 33表位的结构模拟物。当用作免疫原时，B2.1A诱导的抗体识别与AP 33相同的表位和E2残基，最重要的是在小鼠模型中保护免受HCV攻击。
HCV vaccine development is stymied by the high genetic diversity of the virus and the variability of the envelope glycoproteins. One strategy to overcome this is to identify conserved, functionally important regions—such as the epitopes of broadly neutralizing antibodies (bNAbs)—and use these as a basis for structure-based vaccine design. Here, we report an anti-idiotype approach that has generated an antibody that mimics a highly conserved neutralizing epitope on HCV E2. Crucially, a mutagenesis screen was used to identify the antibody, designated B2.1 A, whose binding characteristics to the bNAb AP33 closely resemble those of the original antigen. Protein crystallography confirmed that B2.1 A is a structural mimic of the AP33 epitope. When used as an immunogen B2.1 A induced antibodies that recognized the same epitope and E2 residues as AP33 and most importantly protected against HCV challenge in a mouse model.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
64.8
作者：
Dorner, Marcus;Horwitz, Joshua A.;Robbins, Justin B.;Barry, Walter T.;Feng, Qian;Mu, Kathy;Jones, Christopher T.;Schoggins, John W.;Catanese, Maria Teresa;Burton, Dennis R.;Law, Mansun;Rice, Charles M.;Ploss, Alexander
通讯作者：
Ploss, Alexander
影响因子：
5.6
作者：
Faelber, K;Kirchhofer, D;Muller, YA
通讯作者：
Muller, YA
影响因子：
5.4
作者：
Gu, Jun;Hardy, Joshua;Drummer, Heidi E.
通讯作者：
Drummer, Heidi E.
人类单克隆抗体MBL-HCV1延迟肝移植后HCV病毒反弹：一项随机对照研究。
DOI：
10.1111/ajt.12083
发表时间：
2013-04
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Chung RT;Gordon FD;Curry MP;Schiano TD;Emre S;Corey K;Markmann JF;Hertl M;Pomposelli JJ;Pomfret EA;Florman S;Schilsky M;Broering TJ;Finberg RW;Szabo G;Zamore PD;Khettry U;Babcock GJ;Ambrosino DM;Leav B;Leney M;Smith HL;Molrine DC
通讯作者：
Molrine DC