RESUMEN
SARS-CoV-2 is currently causing a devastating pandemic and there is a pressing need to understand the dynamics, specificity, and neutralizing potency of the humoral immune response during acute infection. Herein, we report the dynamics of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in 44 COVID-19 patients. RBD-specific IgG responses were detectable in all patients 6 days after PCR confirmation. Using a clinical isolate of SARS-CoV-2, neutralizing antibody titers were also detectable in all patients 6 days after PCR confirmation. The magnitude of RBD-specific IgG binding titers correlated strongly with viral neutralization. In a clinical setting, the initial analysis of the dynamics of RBD-specific IgG titers was corroborated in a larger cohort of PCR-confirmed patients (n=231). These findings have important implications for our understanding of protective immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of much-needed vaccines.
RESUMEN
The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor-binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 - 0.05 g/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.