ABSTRACT Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484, and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and variants of concern (VOCs), including B.1.1.7 (alpha), P.1 (gamma), and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting that different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to the first pandemic wave of prototype SARS-CoV-2 possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern.
【저자키워드】 SARS-CoV-2, variants of concern, Infectious disease, monoclonal antibodies, Humoral immunity, breath, Single Cell, immune memory, 【초록키워드】 neutralizing antibody, coronavirus, vaccination, pandemic, Mutation, Immunity, Neutralizing antibodies, antibody, monoclonal antibody, Human, variant, B.1.617.2, monoclonal antibodies, variants, Spike protein, Receptor binding domain, Epitopes, Region, Viral, Transmissibility, B.1.1.7, RBD, P.1, VOCs, Viral variants, Alpha, target, Neutralizing, respiratory, convalescent, natural infection, epitope, Critical, mAbs, Donor, binding, SARS-CoV-2 spike, mAb, (Alpha), acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, K417, prototype, neutralize, affected, the spike protein, induce, disrupt, distinct domain, the SARS-CoV-2, 【제목키워드】 spike, concern, targeting,