Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients’ B Cells

By Yunlong Cao, B. Su, Xianghua Guo, Yongqiang Deng, L. Bao, Qinyu Zhu, Xu Zhang, Yinghui Zheng, Chenyan Geng, Xiaoran Chai and 23 more. Cell, 2020

1,162 citations recorded by the source corpus.

The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1+ clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8 Å cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody’s epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2-neutralizing antibodies could be directly selected based on similarities of their predicted CDR3H structures to those of SARS-CoV-neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B cell sequencing in response to pandemic infectious diseases.

Subfields: Infectious Diseases, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/e8ff6223d6308149a06f372e4a5bebe8667526fd

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Citations in the corpus

Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition (2020, positive): “The escapemutations for themost potently neutralizing antibodies fall mostly in the RBM (Figures 2A and 2C), consistent with prior studies showing that potent anti-RBD neutralizing antibodies often compete with ACE2 binding (Brouwer et al., 2020; Cao et al., 2020; Huang et al., 2020; Ju et al., 2020”
Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, background): “Most neutralizing SARS-CoV-2 mAbs block RBD interactions with ACE2 (Brouwer et al., 2020; Cao et al., 2020; Ju et al., 2020; Liu et al., 2020a; Rogers et al., 2020; Seydoux et al., 2020; Wec et al., 2020; Wu et al., 2020; Zost et al., 2020a, 2020b).”
COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas (2021, neutral): “…Cell 184, 1895–1913, April 1, 2021 Single-cell RNA sequencing (scRNA-seq) is powerful at dissecting the immune responses and has been applied to COVID-19 studies (Cao et al., 2020; Chua et al., 2020; Fan et al., 2020; Su et al., 2020; Wen et al., 2020; Xie et al., 2020; Zhang et al., 2020a, 2020b).”
Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding (2020, positive): “The RBD is the dominant target of neutralizing antibodies (Cao et al., 2020; Ju et al., 2020; Pinto et al., 2020; Rogers et al., 2020; Seydoux et al., 2020; Shi et al., 2020; Wu et al., 2020; Zost et al., 2020), and so any antigenic drift will be constrained by its mutational tolerance.”
SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development (2020, background): “Structural superimposition of SARSCoV-2 RBD/ACE2 complex and SARS-CoV-2 RBD/BD-23 complex shows that BD-23 could clash with ACE2 to inhibit the RBD-ACE2 binding, endowing BD-23 with the SARS-CoV-2 neutralizing ability (Cao et al., 2020).”