Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses.

Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how ...
class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ?1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.
Mesh Terms:
Aged, Angiotensin-Converting Enzyme 2, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antibody Formation, B-Lymphocytes, Binding Sites, COVID-19, Chlorocebus aethiops, Cryoelectron Microscopy, HEK293 Cells, Humans, Immunoglobulin Heavy Chains, Immunoglobulin Light Chains, Male, Protein Binding, Protein Interaction Domains and Motifs, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vero Cells
Cell Rep
Date: Oct. 05, 2021
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