Abstract
Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.
Keywords: B-cell; SARS-CoV-2; biotechnology; immunity; neutralization; public antibody; virology; yeast display.
【저자키워드】 SARS-CoV-2, Virology, Immunity, neutralization, Biotechnology, B-cell, public antibody, yeast display., 【초록키워드】 Structure, ACE2, Vaccine, antibody, neutralization, Antibody Response, monoclonal antibody, Genetic, B cells, immune, Prevalence, Therapeutic strategies, understanding, mechanism, therapeutic strategy, yeast, SARS-CoV-2 neutralization, cryo-EM structures, Protective, Protective antibody, convalescent COVID-19 patients, sequence, sequence similarity, member, precursor, binding interactions, medical intervention, cryo, spike trimer, Genes, feature, SARS-CoV-2 spike trimer, highlight, binding interaction, develop, functional, determine, analysis, the SARS-CoV-2, 【제목키워드】 Antibody Response, contribute,