Effects of prior COVID-19 infection on B cell repertoire response to SARS-CoV-2 vaccination

We sequenced the B cell receptor repertoire (heavy-chain) of individuals undergoing vaccination by SARS-CoV-2 mRNA vaccine (Comirnaty/Pfizer/BNT162b2) with (seropositive) or without (seronegative) previous laboratory confirmed COVID-19 infection. We characterized differential isotype usage, V gene usage, HCD3R length, percentage of somatic hypermutation, and clonotype diversity. Only somatic hypermutation showed differential response to vaccination. We then characterized vaccine-expanded clonotypes and found that seropositive vaccine-expanded clonotypes had higher somatic hypermutation than seronegative vaccine-expanded clonotypes; and expanded clone groups for both serotypes had CDR3 lengths that were shorter than the rest of the repertoire. Moreover, in both groups we identified public clonotypes that were shared (2 or more individuals), including 28 clonotypes that were present in every sample tested in this study. We aligned HCDR3 regions of shared clonotypes and vaccine-expanded clonotypes to the Covid antibody data base (CoV-ab-dab) and had multiple matches, indicating clonal convergence in response to the vaccine.

本研究对接种SARS-CoV-2 mRNA疫苗（Comirnaty/辉瑞/BNT162b2）的个体进行B细胞受体重链库（B cell receptor repertoire, heavy-chain）测序，受试对象分为两组：既往经实验室确诊感染新型冠状病毒肺炎（COVID-19）的血清阳性（seropositive）组，以及未感染过新冠病毒的血清阴性（seronegative）组。本研究分析了两组在抗体同种型使用、V基因使用、HCD3R长度、体细胞超突变（somatic hypermutation）比例以及克隆型多样性（clonotype diversity）上的组间差异，结果显示仅体细胞超突变呈现出疫苗响应的组间差异。随后本研究对疫苗扩增克隆型进行表征，发现血清阳性组的疫苗扩增克隆型的体细胞超突变水平显著高于血清阴性组；且两组的扩增克隆群的CDR3长度均较其余B细胞受体库更短。此外，两组中均鉴定出公共克隆型（public clonotypes，即2名及以上个体共有的克隆型），其中包含28种在本研究全部检测样本中均存在的克隆型。本研究将共享克隆型与疫苗扩增克隆型的HCDR3区域与新冠抗体数据库（CoV-ab-dab）进行序列比对，获得多个匹配结果，表明机体针对该疫苗接种产生了克隆趋同免疫应答。