Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors
| العنوان: | Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors |
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| المؤلفون: | Meital Gal-Tanamy, Smadar Hada-Neeman, Modi Safra, Anna Roitburd-Berman, Hila Sharim, Michael Mor, David Hagin, Sandra L Leibel, Ben A. Croker, Aaron F. Carlin, Ksenia Polonsky, Joel Alter, Dor Rafael, Eric R. Griffis, Gur Yaari, Michal Werbner, Oren Zimhony, Alex E. Clark, Michal Navon, Noam Ben-Shalom, Elad Chomsky, Moshe Dessau, Oren Kobiler, Natalia T. Freund, Cameron J. Nowell, Evgeny Kiner, Jamie C. Lee, Jonathan M. Gershoni |
| المصدر: | PLoS Pathogens, Vol 17, Iss 2, p e1009165 (2021) PLoS Pathogens bioRxiv article-version (status) pre article-version (number) 1 |
| بيانات النشر: | Public Library of Science (PLoS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, RNA viruses, Viral Diseases, B Cells, Coronaviruses, Physiology, Antibody Response, Antibodies, Viral, Biochemistry, Epitope, Epitopes, White Blood Cells, Medical Conditions, 0302 clinical medicine, Animal Cells, Immune Physiology, Chlorocebus aethiops, Cloning, Molecular, Enzyme-Linked Immunoassays, Biology (General), Immune Response, Pathology and laboratory medicine, Staining, 0303 health sciences, education.field_of_study, Immune System Proteins, biology, breakpoint cluster region, Antibodies, Monoclonal, Cell Staining, Middle Aged, Medical microbiology, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Viruses, Female, SARS CoV 2, Pathogens, Cellular Types, Antibody, Research Article, Adult, SARS coronavirus, QH301-705.5, Immune Cells, Immunology, B-cell receptor, Population, Research and Analysis Methods, Microbiology, Article, Antibodies, 03 medical and health sciences, Immune system, Virology, Genetics, medicine, Animals, Humans, Antibody-Producing Cells, Immunoassays, Molecular Biology Techniques, education, Vero Cells, Molecular Biology, B cell, Aged, 030304 developmental biology, Medicine and health sciences, Blood Cells, Biology and life sciences, SARS-CoV-2, Organisms, Viral pathogens, COVID-19, Proteins, Convalescence, Covid 19, Cell Biology, RC581-607, Antibodies, Neutralizing, Microbial pathogens, Epitope mapping, Specimen Preparation and Treatment, Immunoglobulin G, Immunologic Techniques, biology.protein, Parasitology, Immunologic diseases. Allergy, Epitope Mapping, Cloning |
| الوصف: | The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe, and not mild, infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19. Author summary The correlates of effective durable antibody response to SARS-CoV-2 infection are still unclear. In this study, we compared B cell receptor signatures in 8 Severe versus 10 Mild SARS-CoV-2 infected Israeli donors, at 1.5 months post infection using molecular and bioinformatic approaches. We found distinct features between the two groups with higher anti-SARS-CoV-2 receptor binding domain (RBD) plasma IgG titers and increased B cell expansion in donors with severe disease manifestations. We further isolated 22 monoclonal antibodies from these donors, 6 of which were highly potent neutralizing the live virus and inhibited the fusion of infected cells. Using mutagenesis and peptide libraries we mapped the binding sites of the neutralizing antibodies on the RBD of the SARS-CoV-2 Spike. We next demonstrated that combinations of different classes of neutralizing mAbs can completely block the live virus from spreading in culture. Lastly, we performed a bioinformatic search in 49 healthy BCR repertoires identifying precursors for these neutralizing antibodies in the top 30 most common precursors, suggesting that these antibodies can be readily produced by the majority of the uninfected population upon antigenic stimulation. |
| تدمد: | 1553-7374 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eaa07acadcd6d8c3ddd335edf971ba70Test https://doi.org/10.1371/journal.ppat.1009165Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....eaa07acadcd6d8c3ddd335edf971ba70 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 |
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