小柯机器人

美国麻省理工学院Ramnik J. Xavier、加州理工学院Pamela J. Bjorkman等研究人员合作揭示SARS-CoV-2变体和SARS-CoV交叉中和背后的B细胞基因组学。2021年4月23日，国际知名学术期刊《细胞》在线发表了这一成果。

研究人员结合了B细胞分选与单细胞VDJ和RNA-seq和单克隆抗体（mAb）结构来表征B细胞对SARS-CoV-2的反应。研究人员发现，SARS-CoV-2特异性B细胞谱系由转录不同的B细胞群体组成，其中具有产生有效中和抗体（nAb）的细胞，这些抗体位于类似于记忆和激活B细胞的两个聚类中。从这两个与SARS-CoV-2突刺三聚体复合的聚类中选择的nAb的冷冻电镜结构显示出对各种受体结合域（RBD）表位的识别。

这些单克隆抗体之一BG10-19可以将突刺三聚体锁定在封闭的构型中，从而有效中和SARS-CoV-2，最近出现的突变体B.1.1.7和B.1.351，以及SARS-CoV并与异源RBD交叉反应。总之，这些结果表征了SARS-CoV-2特异性B细胞之间的转录差异，并揭示了交叉中和的Ab靶标，从而为靶向冠状病毒的免疫原和治疗设计提供了依据。

据了解，mAb是疫苗和治疗设计中的重点，可抵抗SARS-CoV-2及其变体。

附：英文原文

Title: B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV

Author: Johannes F. Scheid, Christopher O. Barnes, Basak Eraslan, Andrew Hudak, Jennifer R. Keeffe, Lisa A. Cosimi, Eric M. Brown, Frauke Muecksch, Yiska Weisblum, Shuting Zhang, Toni Delorey, Ann E. Woolley, Fadi Ghantous, Sung-Moo Park, Devan Phillips, Betsabeh Tusi, Kathryn E. Huey-Tubman, Alexander A. Cohen, Priyanthi N.P. Gnanapragasam, Kara Rzasa, Theodora Hatziioanno, Michael A. Durney, Xiebin Gu, Takuya Tada, Nathaniel R. Landau, Anthony P. West, Orit Rozenblatt-Rosen, Michael S. Seaman, Lindsey R. Baden, Daniel B. Graham, Jacques Deguine, Paul D. Bieniasz, Aviv Regev, Deborah Hung, Pamela J. Bjorkman, Ramnik J. Xavier

Issue&Volume: 2021-04-23

Abstract: Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract SARS-CoV-2 and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA-seq and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.

DOI: 10.1016/j.cell.2021.04.032

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00535-3