Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike

Timothy J C Tan; Abhishek K Verma; Abby Odle; Ruipeng Lei; David K Meyerholz; Kenneth A Matreyek; Stanley Perlman; Lok-Yin Roy Wong; Nicholas C Wu

doi:10.1073/pnas.2317222121

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Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike

Journal article

Open access

Peer reviewed

Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike

Timothy J C Tan, Abhishek K Verma, Abby Odle, Ruipeng Lei, David K Meyerholz, Kenneth A Matreyek, Stanley Perlman, Lok-Yin Roy Wong and Nicholas C Wu

Proceedings of the National Academy of Sciences - PNAS, Vol.121(15), e2317222121

04/09/2024

DOI: 10.1073/pnas.2317222121

PMCID: PMC11009667

PMID: 38557175

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https://doi.org/10.1073/pnas.2317222121View

Published (Version of record) Open Access

Abstract

Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding domain of spike protein. In contrast, whether antigenic drift occurs in the S2 domain remains largely elusive. Here, we perform a deep mutational scanning experiment to identify S2 mutations that affect binding of SARS-CoV-2 spike to three S2 apex public antibodies. Our results indicate that spatially diverse mutations, including D950N and Q954H, which are observed in Delta and Omicron variants, respectively, weaken the binding of spike to these antibodies. Although S2 apex antibodies are known to be nonneutralizing, we show that they confer protection in vivo through Fc-mediated effector functions. Overall, this study indicates that the S2 domain of SARS-CoV-2 spike can undergo antigenic drift, which represents a potential challenge for the development of more universal coronavirus vaccines.

Antibodies

Antibodies, Viral

Antigenic Drift and Shift

COVID-19

Humans

SARS-CoV-2 - genetics

Spike Glycoprotein, Coronavirus - genetics

Details

Title: Subtitle: Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike
Creators: Timothy J C Tan - University of Illinois Urbana-Champaign
Abhishek K Verma - University of Iowa
Abby Odle - University of Iowa
Ruipeng Lei - University of Illinois Urbana-Champaign
David K Meyerholz - University of Iowa
Kenneth A Matreyek - Case Western Reserve University
Stanley Perlman - University of Iowa
Lok-Yin Roy Wong - University of Iowa
Nicholas C Wu - University of Illinois Urbana-Champaign
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.121(15), e2317222121
DOI: 10.1073/pnas.2317222121
PMID: 38557175
PMCID: PMC11009667
eISSN: 1091-6490
Grant note: R01 AI165475 / NIAID NIH HHS K99 AI170996 / NIAID NIH HHS
Language: English
Date published: 04/09/2024
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984582304802771

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