Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies.
Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies.
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靶向抗二动抗体的免疫原的VRC01级种系的开发。
DOI：
10.1016/j.celrep.2021.109084
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发表时间：
2021-05-04
期刊：
影响因子：
8.8
通讯作者：
McGuire AT
中科院分区：
文献类型：
--
作者：
Seydoux E;Wan YH;Feng J;Wall A;Aljedani S;Homad LJ;MacCamy AJ;Weidle C;Gray MD;Brumage L;Taylor JJ;Pancera M;Stamatatos L;McGuire AT
一种有效的HIV-1疫苗可能需要诱导广泛的中和抗体(BNAbs)。广泛而有效的VRC01类bNAb已经从多个感染个体中分离出来，这表明它们可以通过疫苗接种而被重复诱导。几种HIV-1包膜来源的生殖系靶向免疫原已被设计成与幼稚的VRC01类前体B细胞结合。然而，它们也提供了非靶点表位，可能会阻碍VRC01类bNAbs的发展。我们鉴定了一组针对推测胚系(IGL)VRC01类抗体的抗独特型单抗(ai-mAbbs)。通过利用结合、结构和B细胞分选数据，我们设计了一个来自两个aimAbb的双特异性分子；一个专用于VRC01类重链，另一个专用于VRC01类轻链。该双功能分子在体外优先激活IGL-VRC01B细胞，并在具有不同多克隆B细胞系的小鼠过继转移模型中诱导特异性抗体反应。该分子代表了另一种非包膜来源的生殖系靶向免疫原，可以在体内选择性地激活VRC01类前体。成功接触幼稚的B细胞，产生广泛的中和抗体，被认为是成功的HIV-1疫苗的关键。在这项研究中，Seydoux等人。介绍了针对VRC01类B细胞前体的抗独特型抗体的特征和评估。他们的结果代表了非包膜来源免疫原的另一种选择。
An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several HIV-1 envelope-derived germline-targeting immunogens have been designed to engage naive VRC01-class precursor B cells. However, they also present off-target epitopes that could hinder development of VRC01-class bNAbs. We characterize a panel of anti-idiotypic monoclonal antibodies (ai-mAbs) raised against inferred-germline (iGL) VRC01-class antibodies. By leveraging binding, structural, and B cell sorting data, we engineered a bispecific molecule derived from two aimAbs; one specific for VRC01-class heavy chains and one specific for VRC01-class light chains. The bispecific molecule preferentially activates iGL-VRC01 B cells in vitro and induces specific antibody responses in a murine adoptive transfer model with a diverse polyclonal B cell repertoire. This molecule represents an alternative non-envelope-derived germline-targeting immunogen that can selectively activate VRC01-class precursors in vivo. Successful engagement of naive B cells that give rise to broadly neutralizing antibodies is thought to be key to a successful HIV-1 vaccine. In this study, Seydoux et al. present the characterization and assessment of anti-idiotypic antibodies targeting VRC01-class B cell precursors. Their results represent an alternative to non-envelope-derived immunogens.
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影响因子：
64.5
作者：
Briney, Bryan;Sok, Devin;Jardine, Joseph G.;Kulp, Daniel W.;Skog, Patrick;Menis, Sergey;Jacak, Ronald;Kalyuzhniy, Oleksandr;de Val, Natalia;Sesterhenn, Fabian;Le, Khoa M.;Ramos, Alejandra;Jones, Meaghan;Saye-Francisco, Karen L.;Blane, Tanya R.;Spencer, Skye;Georgeson, Erik;Hu, Xiaozhen;Ozorowski, Gabriel;Adachi, Yumiko;Kubitz, Michael;Sarkar, Anita;Wilson, Ian A.;Ward, Andrew B.;Nemazee, David;Burton, Dennis R.;Schief, William R.
通讯作者：
Schief, William R.
影响因子：
32.4
作者：
Falkowska, Emilia;Le, Khoa M.;Ramos, Alejandra;Doores, Katie J.;Lee, Jeong Hyun;Blattner, Claudia;Ramirez, Alejandro;Derking, Ronald;van Gils, Marit J.;Liang, Chi-Hui;Mcbride, Ryan;von Bredow, Benjamin;Shivatare, Sachin S.;Wu, Chung-Yi;Chan-Hui, Po-Ying;Liu, Yan;Feizi, Ten;Zwick, Michael B.;Koff, Wayne C.;Seaman, Michael S.;Swiderek, Kristine;Moore, John P.;Evans, David;Paulson, James C.;Wong, Chi-Huey;Ward, Andrew B.;Wilson, Ian A.;Sanders, Rogier W.;Poignard, Pascal;Burton, Dennis R.
通讯作者：
Burton, Dennis R.
影响因子：
3.7
作者：
Corti D;Langedijk JP;Hinz A;Seaman MS;Vanzetta F;Fernandez-Rodriguez BM;Silacci C;Pinna D;Jarrossay D;Balla-Jhagjhoorsingh S;Willems B;Zekveld MJ;Dreja H;O'Sullivan E;Pade C;Orkin C;Jeffs SA;Montefiori DC;Davis D;Weissenhorn W;McKnight A;Heeney JL;Sallusto F;Sattentau QJ;Weiss RA;Lanzavecchia A
通讯作者：
Lanzavecchia A
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
15.3
作者：
Dosenovic, Pia;Pettersson, Anna-Klara;McGuire, Andrew T.
通讯作者：
McGuire, Andrew T.