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The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Liu, Chang, Zhou, Daming, Nutalai, Rungtiwa, Duyvesteyn, Helen M.E., Tuekprakhon, Aekkachai, Ginn, Helen M., Dejnirattisai, Wanwisa, Supasa, Piyada, Mentzer, Alexander J., Wang, Beibei, and others. (2021) The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants. Cell Host & Microbe, . ISSN 1931-3128. E-ISSN 1934-6069. (doi:10.1016/j.chom.2021.11.013) (KAR id:91956)

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Official URL:
https://doi.org/10.1016/j.chom.2021.11.013

Abstract

Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1 and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor binding domain (RBD). Two of these RBD-binding mAbs recognise a neutralizing epitope conserved between SARS-CoV-1 and -2, whilst 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

Item Type: Article
DOI/Identification number: 10.1016/j.chom.2021.11.013
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 02 Dec 2021 22:26 UTC
Last Modified: 03 Dec 2021 11:45 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/91956 (The current URI for this page, for reference purposes)
Temperton, Nigel: https://orcid.org/0000-0002-7978-3815
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