A neutralizing epitope on the SD1 domain of SARS-CoV-2 spike targeted following infection and vaccination
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Jeffrey Seow Hataf Khan Annachiara Rosa Valeria Calvaresi Carl Graham Suzanne Pickering Val Pye Nora B Cronin Isabella Huettner Michael H Malim Argyris Politis Peter Cherepanov Katie J DooresAbstract
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.
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Publisher website (DOI) 10.1016/j.celrep.2022.111276
Europe PubMed Central 35981534
Pubmed 35981534
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