EMD-26217
Negative stain EM map of COVA1-07 mAb bound to the S2 domain of SARS-CoV-2 S
EMD-26217
Single-particle18.5 Å
Deposition: 16/02/2022Map released: 06/07/2022
Last modified: 17/08/2022
Sample Organism:
Homo sapiens
Sample: Negative stain EM map of COVA2-18 mAb bound to the S2 domain of SARS-CoV-2 S
Deposition Authors: Han J
,
Ward AB
Sample: Negative stain EM map of COVA2-18 mAb bound to the S2 domain of SARS-CoV-2 S
Deposition Authors: Han J
,
Ward AB
A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike.
Claireaux M ,
Caniels TG ,
de Gast M,
Han J ,
Guerra D ,
Kerster G,
van Schaik BDC,
Jongejan A ,
Schriek AI,
Grobben M ,
Brouwer PJM,
van der Straten K ,
Aldon Y ,
Capella-Pujol J ,
Snitselaar JL,
Olijhoek W,
Aartse A,
Brinkkemper M,
Bontjer I ,
Burger JA,
Poniman M,
Bijl TPL,
Torres JL ,
Copps J ,
Martin IC ,
de Taeye SW,
de Bree GJ,
Ward AB ,
Sliepen K ,
van Kampen AHC,
Moerland PD ,
Sanders RW ,
van Gils MJ
(2022) Nat Commun , 13 , 4539 - 4539
,
Caniels TG ,
de Gast M,
Han J ,
Guerra D ,
Kerster G,
van Schaik BDC,
Jongejan A ,
Schriek AI,
Grobben M ,
Brouwer PJM,
van der Straten K ,
Aldon Y ,
Capella-Pujol J ,
Snitselaar JL,
Olijhoek W,
Aartse A,
Brinkkemper M,
Bontjer I ,
Burger JA,
Poniman M,
Bijl TPL,
Torres JL ,
Copps J ,
Martin IC ,
de Taeye SW,
de Bree GJ,
Ward AB ,
Sliepen K ,
van Kampen AHC,
Moerland PD ,
Sanders RW ,
van Gils MJ
(2022) Nat Commun , 13 , 4539 - 4539
Abstract:
Delineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigate the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We show that ∼82% of SARS-CoV-2 S-reactive B cells harbor a naive phenotype, which represents an unusually high fraction of total human naive B cells (∼0.1%). Approximately 10% of these naive S-reactive B cells share an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre-fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines.
Delineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigate the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We show that ∼82% of SARS-CoV-2 S-reactive B cells harbor a naive phenotype, which represents an unusually high fraction of total human naive B cells (∼0.1%). Approximately 10% of these naive S-reactive B cells share an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre-fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines.