In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 2 ( 2021-2-11), p. e1009165-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009165
DOI:
10.1371/journal.ppat.1009165.g001
DOI:
10.1371/journal.ppat.1009165.g002
DOI:
10.1371/journal.ppat.1009165.g003
DOI:
10.1371/journal.ppat.1009165.g004
DOI:
10.1371/journal.ppat.1009165.g005
DOI:
10.1371/journal.ppat.1009165.g006
DOI:
10.1371/journal.ppat.1009165.g007
DOI:
10.1371/journal.ppat.1009165.s001
DOI:
10.1371/journal.ppat.1009165.s002
DOI:
10.1371/journal.ppat.1009165.s003
DOI:
10.1371/journal.ppat.1009165.s004
DOI:
10.1371/journal.ppat.1009165.s005
DOI:
10.1371/journal.ppat.1009165.s006
DOI:
10.1371/journal.ppat.1009165.s007
DOI:
10.1371/journal.ppat.1009165.s008
DOI:
10.1371/journal.ppat.1009165.s009
DOI:
10.1371/journal.ppat.1009165.s010
DOI:
10.1371/journal.ppat.1009165.s011
DOI:
10.1371/journal.ppat.1009165.s012
DOI:
10.1371/journal.ppat.1009165.s013
DOI:
10.1371/journal.ppat.1009165.s014
DOI:
10.1371/journal.ppat.1009165.s015
DOI:
10.1371/journal.ppat.1009165.s016
DOI:
10.1371/journal.ppat.1009165.r001
DOI:
10.1371/journal.ppat.1009165.r002
DOI:
10.1371/journal.ppat.1009165.r003
DOI:
10.1371/journal.ppat.1009165.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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