美国华盛顿大学Leonidas Stamatatos和斯坦福大学Po-Ssu Huang美国疫苗和传染病科Marie Pancera研究组合作取得一项新突破。他们揭示HIV-1 VRC01生殖细胞靶向免疫原选择不同的表位特异性B细胞受体。2020年10月13日出版的《免疫》杂志发表了这项成果。

他们比较了三种靶向特定生殖细胞免疫原的能力，这是一种在表达生殖细胞VH和VRC01抗体和多种小鼠轻链的转基因小鼠中针对VRC01类受体的免疫原，它能够激活特定的B细胞。在免疫后，不同时间点的免疫原特异性的VRC01样B细胞被分离出来，对其VH和VL基因进行测序，并鉴定相应的抗体。具有不同交叉反应性的VRC01 B细胞亚群被每种免疫原激活，这些差异与针对生殖细胞的免疫原的独特生物物理和生化特征相关。

他们的研究表明，设计有效的免疫原来激活产生保护性HIV-1抗体的B细胞受体方法，需要更好地了解针对生殖细胞免疫原的抗原决定簇及其周围表面的生物物理特性，如何影响特定生殖细胞免疫原和可用体内受体变体的相互作用。

研究人员表示，HIV-1广泛中和抗体的激活前体B细胞受体需要专门设计的免疫原。

附：英文原文

Title: HIV-1 VRC01 Germline-Targeting Immunogens Select Distinct Epitope-Specific B Cell Receptors

Author: Yu-Ru Lin, K. Rachael Parks, Connor Weidle, Anika S. Naidu, Arineh Khechaduri, Andrew O. Riker, Brittany Takushi, Jung-Ho Chun, Andrew J. Borst, David Veesler, Andrew Stuart, Parul Agrawal, Matthew Gray, Marie Pancera, Po-Ssu Huang, Leonidas Stamatatos

Issue&Volume: 2020/10/13

Abstract: Activating precursor B cell receptors of HIV-1 broadly neutralizing antibodies requiresspecifically designed immunogens. Here, we compared the abilities of three such germline-targetingimmunogens against the VRC01-class receptors to activate the targeted B cells in transgenicmice expressing the germline VH of the VRC01 antibody but diverse mouse light chains.Immunogen-specific VRC01-like B cells were isolated at different time points afterimmunization, their VH and VL genes were sequenced, and the corresponding antibodiescharacterized. VRC01 B cell sub-populations with distinct cross-reactivity propertieswere activated by each immunogen, and these differences correlated with distinct biophysicaland biochemical features of the germline-targeting immunogens. Our study indicatesthat the design of effective immunogens to activate B cell receptors leading to protectiveHIV-1 antibodies will require a better understanding of how the biophysical propertiesof the epitope and its surrounding surface on the germline-targeting immunogen influenceits interaction with the available receptor variants in vivo.

DOI: 10.1016/j.immuni.2020.09.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30401-5