This report describes the discovery and characterization of antibodies with potential broad SARS-CoV-2 neutralization profiles. The antibodies were obtained from a phage display library built with the VH repertoire of a convalescent COVID-19 patient who was infected with SARS-CoV-2 B.1.617.2 (Delta). The patient received a single dose of Ad5-nCoV vaccine (Convidecia™, CanSino Biologics Inc.) one month before developing COVID-19 symptoms. Four synthetic VL libraries were used as counterparts of the immune VH repertoire. After three rounds of panning with SARS-CoV-2 receptor-binding domain wildtype (RBD-WT) 34 unique scFvs, were identified, with 27 cross-reactive for the RBD-WT and RBD Delta (RBD-DT), and seven specifics for the RBD-WT. The cross-reactive scFvs were more diverse than the RBD-WT specific ones, being encoded by several IGHV genes from the IGHV1 and IGHV3 families combined with short HCDR3s. Six cross-reactive scFvs and one RBD-WT specific scFv were converted to human IgG1 (hIgG1). Out of the seven antibodies, six blocked the RBD-WT binding to angiotensin converting enzyme 2 (ACE2), suggesting these antibodies may neutralize the SARS-CoV-2 infection. Importantly, one of the antibodies also recognized the RBD from the B.1.1.529 (Omicron) isolate, implying that the VH repertoire of the convalescent patient would protect against SARS-CoV-2 Wildtype, Delta, and Omicron. From a practical viewpoint, the triple cross-reactive antibody provides the substrate for developing therapeutic antibodies with a broad SARS-CoV-2 neutralization profile.
【저자키워드】 COVID-19, VOCs, Receptor-binding domain (RBD), phage display, therapeutic antibodies, 【초록키워드】 antibodies, SARS-CoV-2, ACE2, Vaccine, antibody, Infection, Delta, B.1.617.2, omicron, immune, RBD, therapeutic, Patient, B.1.1.529, convalescent, COVID-19 symptoms, SARS-CoV-2 neutralization, convalescent patient, single dose, binding, COVID-19 patient, cross-reactive, cross-reactive antibody, enzyme, domain, profiles, wildtype, scFv, neutralize, human IgG1, Seven, PROTECT, blocked, provide, were used, unique, the RBD, IGHV, Inc., infected with SARS-CoV-2, the antibody, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, Delta, omicron, library, phage, display, Isolated,