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

Cell Host Microbe. 2021 Nov 27:S1931-3128(21)00519-9. doi: 10.1016/j.chom.2021.11.013. Online ahead of print.ABSTRACTAlpha-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 recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 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.PMID:34921776 | PMC:PMC8626228 | DOI:10.1016/j.chom.2021.11.013

Source: Cell Host and Microbe - December 18, 2021 Category: Microbiology Authors: Chang Liu Daming Zhou Rungtiwa Nutalai Helen M E Duyvesteyn Aekkachai Tuekprakhon Helen M Ginn Wanwisa Dejnirattisai Piyada Supasa Alexander J Mentzer Beibei Wang James Brett Case Yuguang Zhao Donal T Skelly Rita E Chen Sile Ann Johnson Thomas G Ritter Ch Source Type: research