B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV
| العنوان: | B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV |
|---|---|
| المؤلفون: | Lisa A. Cosimi, Betsabeh Khoramian Tusi, Yiska Weisblum, Kathryn E. Huey-Tubman, Andrew Hudak, Alexander A. Cohen, Orit Rozenblatt-Rosen, Lindsey R. Baden, Aviv Regev, Kara Rzasa, Frauke Muecksch, Michael S. Seaman, Xiebin Gu, Christopher O. Barnes, Jennifer R. Keeffe, Ann E. Woolley, Paul D. Bieniasz, Michael A Durney, Priyanthi N. P. Gnanapragasam, Toni Delorey, Anthony P. West, Pamela J. Bjorkman, Sung-Moo Park, Devan Phillips, Takuya Tada, Fadi Ghantous, Johannes Scheid, Deborah T. Hung, Shuting Zhang, Nathaniel R. Landau, Ramnik J. Xavier, Jacques Deguine, Daniel B. Graham, Basak Eraslan, Eric M. Brown, Theodora Hatziioanno |
| المصدر: | Cell |
| بيانات النشر: | Cell Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Immunogen, viruses, Immunoglobulin Variable Region, Antigen-Antibody Complex, Antibodies, Viral, Crystallography, X-Ray, Epitope, Antigen-Antibody Reactions, 0302 clinical medicine, skin and connective tissue diseases, 0303 health sciences, B-Lymphocytes, biology, Antibodies, Monoclonal, virus diseases, medicine.anatomical_structure, Spike Glycoprotein, Coronavirus, monoclonal antibodies, Antibody, medicine.drug_class, Protein domain, Heterologous, cryo-electron microscopy, Monoclonal antibody, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, disordered CDRH3, Protein Domains, memory B cells, medicine, Humans, Protein Structure, Quaternary, B cell, 030304 developmental biology, SARS-CoV cross-neutralization, SARS-CoV-2, Sequence Analysis, RNA, Gene Expression Profiling, fungi, Cryoelectron Microscopy, RNA, COVID-19, Virology, Antibodies, Neutralizing, Immunoglobulin A, body regions, single B cell genomics, biology.protein, Protein Multimerization, 030217 neurology & neurosurgery |
| الوصف: | Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract SARS-CoV-2 and its variants. Here, we combined B cell sorting with single-cell VDJ and 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. B cell genomics reveals transcriptionally distinct populations that modulate antibody responses to SARS-CoV-2, with the identification of a monoclonal antibody that locks the virus spike trimer to neutralize recent variants, SARS and heterologous RBDs. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1620e23fa39fd9c246a23789249c7917 https://resolver.caltech.edu/CaltechAUTHORS:20210429-090704273 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1620e23fa39fd9c246a23789249c7917 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |