ABSTRACT

Dynamic changes of the paired heavy and light chain B cell receptor (BCR) repertoire provide an essential insight into understanding the humoral immune response post-SARS-CoV-2 infection and vaccination. However, differences between the endogenous paired BCR repertoire kinetics in SARS-CoV-2 infection and previously recovered/naïve subjects treated with the inactivated vaccine remain largely unknown. We performed single-cell V(D)J sequencing of B cells from six healthy donors with three shots of inactivated SARS-CoV-2 vaccine (BBIBP-CorV), five people who received the BBIBP-CorV vaccine after having recovered from COVID-19, five unvaccinated COVID-19 recovered patients and then integrated with public data of B cells from four SARS-CoV-2-infected subjects. We discovered that BCR variable (V) genes were more prominently used in the SARS-CoV-2 exposed groups (both in the group with active infection and in the group that had recovered) than in the vaccinated groups. The VH gene that expanded the most after SARS-CoV-2 infection was IGHV3-33, while IGHV3-23 in the vaccinated groups. SARS-CoV-2-infected group enhanced more BCR clonal expansion and somatic hypermutation than the vaccinated healthy group. A small proportion of public clonotypes were shared between the SARS-CoV-2 infected, vaccinated healthy, and recovered groups. Moreover, several public antibodies had been identified against SARS-CoV-2 spike protein. We comprehensively characterize the paired heavy and light chain BCR repertoire from SARS-CoV-2 infection to vaccination, providing further guidance for the development of the next-generation precision vaccine.

摘要

成对的重链和轻链 B 细胞受体 (BCR) 库的动态变化为了解 SARS-CoV-2 感染和疫苗接种后的体液免疫反应提供了重要的见解。然而，在 SARS-CoV-2 感染中的内源性配对 BCR 库动力学与以前用灭活疫苗治疗的恢复/未接受过受试者之间的差异在很大程度上仍然未知。我们用三针灭活 SARS-CoV-2 疫苗 (BBIBP-CorV) 对六名健康供体的 B 细胞进行了单细胞 V(D)J 测序，其中五名从 COVID- 康复后接种了 BBIBP-CorV 疫苗19 日，五名未接种疫苗的 COVID-19 患者康复，然后与来自四名 SARS-CoV-2 感染受试者的 B 细胞的公共数据相结合。我们发现 BCR 变量 (V) 基因在 SARS-CoV-2 暴露组（包括活跃感染组和已康复组）中的使用比在接种组中更为突出。感染 SARS-CoV-2 后扩增最多的 VH 基因是 IGHV3-33，而在接种组中扩增最多的是 IGHV3-23。与接种疫苗的健康组相比，SARS-CoV-2 感染组增强了更多的 BCR 克隆扩增和体细胞超突变。一小部分公共克隆型在 SARS-CoV-2 感染组、接种疫苗的健康组和康复组之间共享。此外，已经鉴定出几种针对 SARS-CoV-2 刺突蛋白的公共抗体。我们全面描述了从 SARS-CoV-2 感染到疫苗接种的配对重链和轻链 BCR 库，