Summary 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 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. Graphical abstract Highlights • Generated 674 antibodies from patients infected with SARS-CoV-2 Beta variant • 18 of 27 most potent mAbs target the 3 mutations in Beta RBD • A major response to N501Y includes a public IgVH4-39 sequence • Two antibodies recognize a neutralizing epitope conserved between SARS-CoV-1 and -2 Liu et al. generated 674 antibodies from patients infected with the SARS-CoV-2 Beta variant. 18 out of 27 most potent neutralizing antibodies isolated target the 3 mutations present in the receptor-binding domain of this variant. This underscores the poor neutralization by Beta serum of early pandemic and Delta viruses.
【저자키워드】 COVID-19, Structure, SARS-CoV-2, Vaccine, antibody, neutralization, Spike protein, Receptor-binding domain, immune responses, Beta variant, 【초록키워드】 viruses, neutralizing antibody, pandemic, Mutation, Neutralizing antibodies, variant, Delta, SARS-CoV-1, Spike protein, serum, Receptor-binding domain, RBD, N501Y, K417N, Patient, E484K, Beta, Neutralizing, escape, NTD, Beta variant, epitope, mAbs, binding, mAb, N-terminal domain, Analysis, Vaccine-induced immunity, Recognition, Abstract, antigenic structure, individual, residue, sequence, multiple mutations, residues, Express, SARS-CoV-2 strain, SARS-CoV-1 and -2, variants of SARS-CoV-2, structure-function, Alter, neutralize, performed, conserved, include, recognize, the spike protein, the receptor-binding domain, mutated, separated, multiple mutation, infected with SARS-CoV-2, the SARS-CoV-2, 【제목키워드】 Antibody Response, antigenic, other variant,