Differences in Allelic Frequency and CDRH3 Region Limit the Engagement of HIV Env Immunogens by Putative VRC01 Neutralizing Antibody Precursors.
Differences in Allelic Frequency and CDRH3 Region Limit the Engagement of HIV Env Immunogens by Putative VRC01 Neutralizing Antibody Precursors.
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等位基因频率和 CDRH3 区域的差异限制了假定的 VRC01 中和抗体前体与 HIV 包膜免疫原的结合。
DOI：
10.1016/j.celrep.2016.10.017
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发表时间：
2016
期刊：
影响因子：
8.8
通讯作者：
Stamatatos,Leonidas
中科院分区：
文献类型：
--
作者：
Yacoob,Christina;Pancera,Marie;Vigdorovich,Vladimir;Oliver,BrianG;Glenn,JoleneA;Feng,Junli;Sather,DNoah;McGuire,AndrewT;Stamatatos,Leonidas
广泛中和抗体的激发仍然是HIV疫苗研究的长期目标。虽然这种抗体可以在HIV-1感染期间产生，但我们对其生殖系，免疫前体形式以及它们与病毒Env相互作用的知识存在差距，限制了我们通过疫苗接种引发它们的能力。对来自VRC 01类的广泛中和抗体的研究提供了对祖B细胞受体（BCR）的深入了解，所述祖B细胞受体（BCR）可以发展成这类抗体。在这里，我们采用高通量重链可变区（VH）/轻链可变区（VL）深度测序，结合生物物理，结构和建模抗体分析，以询问健康个体中循环潜在的VRC 01-祖细胞BCR。我们的研究揭示，并非所有人都同样倾向于产生VRC 01类抗体，并非所有预测的表达VRC 01的祖细胞B细胞都能与Env结合，并且生殖系VRC 01抗体的CDRH 3区域影响它们识别HIV-1的能力。这些发现对于应考虑CDRH 3相互作用的优化免疫原的设计至关重要。
Elicitation of broadly neutralizing antibodies remains a long-standing goal of HIV vaccine research. Although such antibodies can arise during HIV-1 infection, gaps in our knowledge of their germline, pre-immune precursor forms, as well as on their interaction with viral Env, limit our ability to elicit them through vaccination. Studies of broadly neutralizing antibodies from the VRC01-class provide insight into progenitor B cell receptors (BCRs) that could develop into this class of antibodies. Here, we employed high-throughput heavy chain variable region (VH)/light chain variable region (VL) deep sequencing, combined with biophysical, structural, and modeling antibody analyses, to interrogate circulating potential VRC01-progenitor BCRs in healthy individuals. Our study reveals that not all humans are equally predisposed to generate VRC01-class antibodies, not all predicted progenitor VRC01-expressing B cells can bind to Env, and the CDRH3 region of germline VRC01 antibodies influence their ability to recognize HIV-1. These findings will be critical to the design of optimized immunogens that should consider CDRH3 interactions.
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影响因子：
32.4
作者：
Zhou T;Zhu J;Wu X;Moquin S;Zhang B;Acharya P;Georgiev IS;Altae-Tran HR;Chuang GY;Joyce MG;Kwon YD;Longo NS;Louder MK;Luongo T;McKee K;Schramm CA;Skinner J;Yang Y;Yang Z;Zhang Z;Zheng A;Bonsignori M;Haynes BF;Scheid JF;Nussenzweig MC;Simek M;Burton DR;Koff WC;NISC Comparative Sequencing Program;Mullikin JC;Connors M;Shapiro L;Nabel GJ;Mascola JR;Kwong PD
通讯作者：
Kwong PD
DOI：
10.1126/science.1192819
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
Kwong PD
DOI：
10.1126/science.1187659
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Wu X;Yang ZY;Li Y;Hogerkorp CM;Schief WR;Seaman MS;Zhou T;Schmidt SD;Wu L;Xu L;Longo NS;McKee K;O'Dell S;Louder MK;Wycuff DL;Feng Y;Nason M;Doria-Rose N;Connors M;Kwong PD;Roederer M;Wyatt RT;Nabel GJ;Mascola JR
通讯作者：
Mascola JR
影响因子：
32.4
作者：
Kwong PD;Mascola JR
通讯作者：
Mascola JR
影响因子：
3.8
作者：
van Gils, Marit J.;Euler, Zelda;Schuitemaker, Hanneke
通讯作者：
Schuitemaker, Hanneke