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Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors
- Source :
- PLoS Pathogens, Vol 17, Iss 2, p e1009165 (2021), PLoS Pathogens, bioRxiv, article-version (status) pre, article-version (number) 1
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- 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.<br />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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15537374
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- PLOS Pathogens
- Accession number :
- edsair.doi.dedup.....eaa07acadcd6d8c3ddd335edf971ba70