TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology to pair B cell receptor heavy and light chains of SARS-CoV-2 spike protein-binding antibodies derived from enriched antigen-specific memory B cells and bulk antibody-secreting cells. We identified approximately 60,000 productive, in-frame, paired antibody sequences, from which 2,093 antibodies were selected for functional evaluation based on abundance, isotype and patterns of somatic hypermutation. The exceptionally diverse antibodies included RBD-binders with broad neutralizing activity against SARS-CoV-2 variants, and S2-binders with broad specificity against betacoronaviruses and the ability to block membrane fusion. A subset of these RBD- and S2-binding antibodies demonstrated robust protection against challenge in hamster and mouse models. This high-throughput approach can accelerate discovery of diverse, multifunctional antibodies against any target of interest.

中文翻译：

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通过来自大量 B 细胞的 BCR 的高通量天然配对鉴定的针对 SARS-CoV-2 的多模式、广泛中和抗体

TruAB Discovery 是一种整合细胞免疫学、高通量免疫测序、生物信息学和计算生物学的方法，旨在发现用于预防或治疗用途的天然人类抗体。我们采用了之前描述的 pairSEQ 技术，将源自富集抗原特异性记忆 B 细胞和大量抗体分泌细胞的 SARS-CoV-2 刺突蛋白结合抗体的 B 细胞受体重链和轻链配对。我们确定了大约 60,000 个生产性、框内、配对抗体序列，其中 2,093 种抗体被选择用于基于体细胞超突变的丰度、同种型和模式进行功能评估。异常多样化的抗体包括对 SARS-CoV-2 变体具有广泛中和活性的 RBD 结合剂，以及对 β 冠状病毒具有广泛特异性和阻断膜融合能力的 S2 结合剂。这些 RBD 和 S2 结合抗体的一个子集在仓鼠和小鼠模型中显示出对攻击的强大保护作用。这种高通量方法可以加速针对任何目标靶标的多样化、多功能抗体的发现。