B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV.
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Abstract | Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses. |
Year of Publication | 2021
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Journal | Cell
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Volume | 184
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Issue | 12
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Pages | 3205-3221.e24
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Date Published | 2021 06 10
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ISSN | 1097-4172
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DOI | 10.1016/j.cell.2021.04.032
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PubMed ID | 34015271
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PubMed Central ID | PMC8064835
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Grant list | R33 AI122390 / AI / NIAID NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
K08 AI120898 / AI / NIAID NIH HHS / United States
P01 AI138938 / AI / NIAID NIH HHS / United States
R21 AI122390 / AI / NIAID NIH HHS / United States
P50 AI150464 / AI / NIAID NIH HHS / United States
U19 AI142784 / AI / NIAID NIH HHS / United States
DP1 DA046100 / DA / NIDA NIH HHS / United States
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