Pre-existing immunity against SARS-CoV-2 may have critical implications for our understanding of COVID-19 susceptibility and severity. Various studies recently provided evidence of pre-existing T cell immunity against SARS-CoV-2 in unexposed individuals. In contrast, the presence and clinical relevance of a pre-existing B cell immunity remains to be fully elucidated. Here, we provide a detailed analysis of the B cell response to SARS-CoV-2 in unexposed individuals. To this end, we extensively investigated the memory B cell response to SARS-CoV-2 in 150 adults sampled pre-pandemically. Comprehensive screening of donor plasma and purified IgG samples for binding and neutralization in various functional assays revealed no substantial activity against SARS-CoV-2 but broad reactivity to endemic betacoronaviruses. Moreover, we analyzed antibody sequences of 8,174 putatively SARS-CoV-2-reactive B cells on a single cell level and generated and tested 158 monoclonal antibodies. None of the isolated antibodies displayed relevant binding or neutralizing activity against SARS-CoV-2. Taken together, our results show no evidence of relevant pre-existing antibody and B cell immunity against SARS-CoV-2 in unexposed adults.

中文翻译：

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健康成人中没有针对 SARS-CoV-2 的大量预先存在的 B 细胞免疫

针对 SARS-CoV-2 的预先存在的免疫力可能对我们理解 COVID-19 易感性和严重性具有重要意义。最近的多项研究提供了证据，表明未暴露个体中预先存在针对 SARS-CoV-2 的 T 细胞免疫。相比之下，预先存在的 B 细胞免疫的存在和临床相关性仍有待充分阐明。在这里，我们详细分析了未暴露个体中 B 细胞对 SARS-CoV-2 的反应。为此，我们广泛研究了大流行前采样的 150 名成年人对 SARS-CoV-2 的记忆 B 细胞反应。在各种功能测定中对供体血浆和纯化的 IgG 样本进行综合筛选以进行结合和中和，结果显示对 SARS-CoV-2 没有实质性活性，但对地方性 β 冠状病毒有广泛的反应性。而且，我们在单细胞水平上分析了 8,174 个推定的 SARS-CoV-2 反应性 B 细胞的抗体序列，并生成并测试了 158 个单克隆抗体。没有一种分离的抗体显示出针对 SARS-CoV-2 的相关结合或中和活性。综上所述，我们的研究结果表明，在未暴露的成年人中，没有证据表明存在针对 SARS-CoV-2 的相关预先存在的抗体和 B 细胞免疫。