TY - JOUR
T1 - Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors
AU - Mor, Michael
AU - Werbner, Michal
AU - Alter, Joel
AU - Safra, Modi
AU - Chomsky, Elad
AU - Lee, Jamie C.
AU - Hada-Neeman, Smadar
AU - Polonsky, Ksenia
AU - Nowell, Cameron J.
AU - Clark, Alex E.
AU - Roitburd-Berman, Anna
AU - Ben-Shalom, Noam
AU - Navon, Michal
AU - Rafael, Dor
AU - Sharim, Hila
AU - Kiner, Evgeny
AU - Griffis, Eric R.
AU - Gershoni, Jonathan M.
AU - Kobiler, Oren
AU - Leibel, Sandra Lawrynowicz
AU - Zimhony, Oren
AU - Carlin, Aaron F.
AU - Yaari, Gur
AU - Dessau, Moshe
AU - Gal-Tanamy, Meital
AU - Hagin, David
AU - Croker, Ben A.
AU - Freund, Natalia T.
N1 - Publisher Copyright:
Copyright: © 2021 Mor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101491694&partnerID=8YFLogxK
U2 - 10.1371/JOURNAL.PPAT.1009165
DO - 10.1371/JOURNAL.PPAT.1009165
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C2 - 33571304
AN - SCOPUS:85101491694
SN - 1553-7366
VL - 17
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 2
M1 - e1009165
ER -