Abstract
The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope (“supersite”) on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2-neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, forming a genetic cluster representing a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface (TI) and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited the cell-to-cell spread of the virus in culture, and conferred protection in human angiotensin-converting enzyme 2-transgenic (ACE2-transgenic) mice against the SARS-CoV-2 challenge. This study provides insight into antibody targeting of the S protein TI region, suggesting this region may be a site of virus vulnerability.
Keywords: Adaptive immunity; Antigen; Immunoglobulins; Immunology; Virology.
【저자키워드】 immunology, Adaptive immunity, immunoglobulins, Antigen, Virology., 【초록키워드】 COVID-19, neutralizing antibody, SARS-CoV-2, coronavirus, Virology, S protein, antibody, Sequencing, Genetic, virus, B cell, Protein, specificity, Culture, mice, Cluster, NTD, receptor, dominant epitope, Protective, binding, Protective antibody, N-terminal domain, acute respiratory syndrome, human antibody response, human Angiotensin-converting enzyme, trimer, virion, MOST, Cell, Trimers, inhibited, functional, provide, recognize, the receptor-binding domain, representing, the S protein, cell-to-cell spread, IGHV1-24, SARS-CoV-2-neutralizing antibody, single B cell, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, antibody, N-terminal domain, spike trimer, disrupt,