B cell receptor signatures associated with strong and poor SARS-CoV-2 vaccine responses

Breakthrough infection of SARS-CoV-2 is a serious challenge, as increased infections were documented in fully-vaccinated individuals. Recipients with poor antibody response are highly vulnerable to reinfection, whereas those with strong antibody responses achieve sterilizing immunity. Thus far, biomarkers associated with levels of vaccine-elicited antibody response are still lacking. Here, we studied the antibody response of age- and gender-controlled healthy cohort, who received inactivated SARS-CoV-2 vaccines and profiled the B cell receptor repertoires in longitudinally consecutive samples. Upon vaccination, all vaccinated individuals displayed a convergent antibody response with shared common antibody clones and public neutralizing antibodies. Strikingly, poor vaccine-responders are distinguishable from strong vaccine-responders by a biased V-usage before vaccination and IgG to IgM mRNA ratio. These findings reveal molecular signatures associated with the different levels of vaccine-induced antibody response, which could be further developed into biomarkers for the design of vaccination strategies.

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的突破性感染是一项严峻挑战，已有研究证实完全接种疫苗的人群中感染病例有所增加。抗体应答不佳的接种者极易发生再次感染，而抗体应答较强的接种者则可获得清除性免疫（sterilizing immunity）。截至目前，仍缺乏与疫苗诱导抗体应答水平相关的生物标志物。本研究针对接种了灭活严重急性呼吸综合征冠状病毒2型疫苗的、年龄与性别匹配的健康队列，分析其抗体应答情况，并对纵向连续采集的样本中的B细胞受体（B cell receptor, BCR）库进行了特征解析。接种疫苗后，所有接种个体均呈现出趋同的抗体应答模式，存在共有抗体克隆与公共中和抗体。值得注意的是，接种前的V基因取用偏倚与IgG与IgM的mRNA比值，可用于区分弱应答与强应答疫苗接种者。本研究揭示了与疫苗诱导抗体应答水平差异相关的分子特征，这些特征可进一步开发为用于优化疫苗接种策略设计的生物标志物。