1. Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses
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Gabriele Cerutti, Yaroslav Tsybovsky, Bharat Madan, Bailey B. Banach, Matheus Oliveira de Souza, Adam S. Olia, Tongqing Zhou, I-Ting Teng, Yaoxing Huang, Jacy R. Wolfe, Phinikoula S. Katsamba, Peter D. Kwong, Pengfei Wang, Manoj S. Nair, Timothy A. Whitehead, Chen-Hsiang Shen, Ahmed S. Fahad, David D. Ho, Kwok-Yung Yuen, Irene M. Francino-Urdaniz, Brandon J. DeKosky, Jude Bimela, Lihong Liu, Eswar R. Reddem, Amy D. Laflin, Xiaoli Pan, Rajani Nimrania, Lawrence Shapiro, Jian Yu, Alexandra Nazzari, Sheila N. Lopez Acevedo, Paul J. Steiner, Matias Gutiérrez-González, and Yang Luo
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Male ,QH301-705.5 ,medicine.drug_class ,B-cell ,Computational biology ,Biology ,Antibodies, Viral ,Immunoglobulin light chain ,Monoclonal antibody ,Article ,General Biochemistry, Genetics and Molecular Biology ,Neutralization ,Immune system ,Report ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Protein Interaction Domains and Motifs ,yeast display ,Biology (General) ,Binding site ,Vero Cells ,B cell ,Aged ,B-Lymphocytes ,Binding Sites ,SARS-CoV-2 ,Cryoelectron Microscopy ,Antibodies, Monoclonal ,COVID-19 ,neutralization ,Antibodies, Neutralizing ,immunity ,virology ,HEK293 Cells ,medicine.anatomical_structure ,Antibody Formation ,Spike Glycoprotein, Coronavirus ,biology.protein ,Immunoglobulin heavy chain ,Immunoglobulin Light Chains ,Angiotensin-Converting Enzyme 2 ,Antibody ,Immunoglobulin Heavy Chains ,public antibody ,Protein Binding ,biotechnology - Abstract
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., Graphical abstract, Banach et al. report a SARS-CoV-2 neutralizing antibody along with genetic, structural, and functional features of public antibody responses targeting SARS-CoV-2. These data reveal how structural interactions with the SARS-CoV-2 receptor-binding domain correlate with viral neutralization and demonstrate the importance of native antibody heavy:light pairings in convergent antibody responses.
- Published
- 2021
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