Stereotypic Neutralizing VH Clonotypes Against SARS-CoV-2 RBD in COVID-19 Patients and the Healthy Population

In six of seven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, VH clonotypes, encoded by either immunoglobin heavy variable (IGHV)3-53 or IGHV3-66 and immunoglobin heavy joining (IGHJ)6, were identified in IgG1, IgA1, and IgA2 subtypes, with minimal mutations, and could be paired with diverse light chains, resulting in binding to the SARS-CoV-2 receptor-binding domain (RBD). Because most human antibodies against the RBD neutralized the virus by inhibiting host cell entry, we selected one of these clonotypes and demonstrated that it could potently inhibit viral replication. Interestingly, these VH clonotypes pre-existed in six of 10 healthy individuals, predominantly as IgM isotypes, which could explain the expeditious and stereotypic development of these clonotypes among SARS-CoV-2 patients.