tetano
Editor, Senior Moderator
Cell Rep
. 2022 Aug 11;111276.
doi: 10.1016/j.celrep.2022.111276. Online ahead of print.
A neutralizing epitope on the SD1 domain of SARS-CoV-2 spike targeted following infection and vaccination
Jeffrey Seow[SUP] 1 [/SUP], Hataf Khan[SUP] 1 [/SUP], Annachiara Rosa[SUP] 2 [/SUP], Valeria Calvaresi[SUP] 3 [/SUP], Carl Graham[SUP] 1 [/SUP], Suzanne Pickering[SUP] 1 [/SUP], Valerie E Pye[SUP] 2 [/SUP], Nora B Cronin[SUP] 4 [/SUP], Isabella Huettner[SUP] 1 [/SUP], Michael H Malim[SUP] 1 [/SUP], Argyris Politis[SUP] 5 [/SUP], Peter Cherepanov[SUP] 6 [/SUP], Katie J Doores[SUP] 7 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the target for neutralizing antibodies elicited following both infection and vaccination. While extensive research has shown that the receptor binding domain (RBD) and, to a lesser extent, the N-terminal domain (NTD) are the predominant targets for neutralizing antibodies, identification of neutralizing epitopes beyond these regions is important for informing vaccine development and understanding antibody-mediated immune escape. Here, we identify a class of broadly neutralizing antibodies that bind an epitope on the spike subdomain 1 (SD1) and that have arisen from infection or vaccination. Using cryo-electron microscopy (cryo-EM) and hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), we show that SD1-specific antibody P008_60 binds an epitope that is not accessible within the canonical prefusion states of the SARS-CoV-2 spike, suggesting a transient conformation of the viral glycoprotein that is vulnerable to neutralization.
Keywords: CP: Immunology; CP: Microbiology; SARS-CoV-2; antibody; cryogenic electron microscopy; hydrogen-deuterium exchange; neutralizing epitope; omicron; spike subdomain 1.
. 2022 Aug 11;111276.
doi: 10.1016/j.celrep.2022.111276. Online ahead of print.
A neutralizing epitope on the SD1 domain of SARS-CoV-2 spike targeted following infection and vaccination
Jeffrey Seow[SUP] 1 [/SUP], Hataf Khan[SUP] 1 [/SUP], Annachiara Rosa[SUP] 2 [/SUP], Valeria Calvaresi[SUP] 3 [/SUP], Carl Graham[SUP] 1 [/SUP], Suzanne Pickering[SUP] 1 [/SUP], Valerie E Pye[SUP] 2 [/SUP], Nora B Cronin[SUP] 4 [/SUP], Isabella Huettner[SUP] 1 [/SUP], Michael H Malim[SUP] 1 [/SUP], Argyris Politis[SUP] 5 [/SUP], Peter Cherepanov[SUP] 6 [/SUP], Katie J Doores[SUP] 7 [/SUP]
Affiliations
- PMID: 35981534
- DOI: 10.1016/j.celrep.2022.111276
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the target for neutralizing antibodies elicited following both infection and vaccination. While extensive research has shown that the receptor binding domain (RBD) and, to a lesser extent, the N-terminal domain (NTD) are the predominant targets for neutralizing antibodies, identification of neutralizing epitopes beyond these regions is important for informing vaccine development and understanding antibody-mediated immune escape. Here, we identify a class of broadly neutralizing antibodies that bind an epitope on the spike subdomain 1 (SD1) and that have arisen from infection or vaccination. Using cryo-electron microscopy (cryo-EM) and hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), we show that SD1-specific antibody P008_60 binds an epitope that is not accessible within the canonical prefusion states of the SARS-CoV-2 spike, suggesting a transient conformation of the viral glycoprotein that is vulnerable to neutralization.
Keywords: CP: Immunology; CP: Microbiology; SARS-CoV-2; antibody; cryogenic electron microscopy; hydrogen-deuterium exchange; neutralizing epitope; omicron; spike subdomain 1.