Abstract
Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals.
Keywords: SARS-CoV-2; neutralizing antibodies; variants of concern.
【저자키워드】 SARS-CoV-2, Neutralizing antibodies, variants of concern., 【초록키워드】 COVID-19, antibodies, ACE2, Neutralizing antibodies, SARS-CoV-2 pandemic, monoclonal antibody, SARS-CoV-2 variant, B cells, variants of concern, combination therapy, Transmission, Prophylactic, variants, B cell, sensitivity, Neutralizing activity, Viral, Receptor-binding domain, RBD, therapeutic, VOCs, Control, Viral variants, Neutralizing, viral variant, Donor, Fab, Interaction, Vaccine-induced immunity, Efficiency, therapeutic antibodies, opens, surface area, overlapping, immunocompromised individuals, infected individuals, Perspective, complex, SARS-CoV-2-infected individuals, Complete, defined, identify, reduced, the receptor-binding domain, immunocompromised individual, response to vaccination, 【제목키워드】 antibody, SARS-CoV-2 variant, effective,