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Tytuł pozycji:

Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors.

Tytuł:
Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors.
Autorzy:
Mor M; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Werbner M; Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
Alter J; Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
Safra M; Alexander Kofkin Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.
Chomsky E; ImmunAi, New York, New York, United States of America.
Lee JC; School of Medicine, University of California San Diego, La Jolla, California, United States of America.
Hada-Neeman S; George S. Wise Life sciences Faculty, Tel Aviv University, Tel-Aviv, Israel.
Polonsky K; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Nowell CJ; Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia.
Clark AE; School of Medicine, University of California San Diego, La Jolla, California, United States of America.
Roitburd-Berman A; George S. Wise Life sciences Faculty, Tel Aviv University, Tel-Aviv, Israel.
Ben-Shalom N; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Navon M; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Rafael D; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Sharim H; ImmunAi, New York, New York, United States of America.
Kiner E; ImmunAi, New York, New York, United States of America.
Griffis ER; Nikon Imaging Center, University of California San Diego, California, United States of America.
Gershoni JM; George S. Wise Life sciences Faculty, Tel Aviv University, Tel-Aviv, Israel.
Kobiler O; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Leibel SL; School of Medicine, University of California San Diego, La Jolla, California, United States of America.
Zimhony O; Kaplan Medical Center, Rehovot, Israel.
Carlin AF; School of Medicine, University of California San Diego, La Jolla, California, United States of America.
Yaari G; Alexander Kofkin Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.
Dessau M; Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
Gal-Tanamy M; Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
Hagin D; Ichilov Hospital, Tel-Aviv, Israel.
Croker BA; School of Medicine, University of California San Diego, La Jolla, California, United States of America.
Freund NT; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Źródło:
PLoS pathogens [PLoS Pathog] 2021 Feb 11; Vol. 17 (2), pp. e1009165. Date of Electronic Publication: 2021 Feb 11 (Print Publication: 2021).
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: San Francisco, CA : Public Library of Science, c2005-
MeSH Terms:
Antibodies, Monoclonal*/genetics
Antibodies, Monoclonal*/immunology
Antibodies, Neutralizing*/genetics
Antibodies, Neutralizing*/immunology
Antibodies, Viral*/genetics
Antibodies, Viral*/immunology
COVID-19*/genetics
COVID-19*/immunology
Convalescence*
SARS-CoV-2*/immunology
Spike Glycoprotein, Coronavirus*/genetics
Spike Glycoprotein, Coronavirus*/immunology
Adult ; Aged ; Animals ; Chlorocebus aethiops ; Cloning, Molecular ; Epitope Mapping ; Epitopes/genetics ; Epitopes/immunology ; Female ; Humans ; Immunoglobulin G/genetics ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Vero Cells
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Grant Information:
R01 HL124209 United States HL NHLBI NIH HHS; United Kingdom WT_ Wellcome Trust
Substance Nomenclature:
0 (Antibodies, Monoclonal)
0 (Antibodies, Neutralizing)
0 (Antibodies, Viral)
0 (Epitopes)
0 (Immunoglobulin G)
0 (Spike Glycoprotein, Coronavirus)
0 (spike protein, SARS-CoV-2)
Entry Date(s):
Date Created: 20210211 Date Completed: 20210222 Latest Revision: 20231104
Update Code:
20240104
PubMed Central ID:
PMC7877634
DOI:
10.1371/journal.ppat.1009165
PMID:
33571304
Czasopismo naukowe
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.
Competing Interests: The authors have declared that no competing interests exist The antibodies described in this manuscript are protected by patent and NT Freund and M Mor and D Hagin are the inventors.
Update of: bioRxiv. 2020 Oct 06;:. (PMID: 33052341)
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