Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation

• Published in: Immunity (Cambridge, Mass.) Vol. 53; no. 1; pp. 98 - 105.e5
• Main Authors: Seydoux, Emilie, Homad, Leah J., MacCamy, Anna J., Parks, K. Rachael, Hurlburt, Nicholas K., Jennewein, Madeleine F., Akins, Nicholas R., Stuart, Andrew B., Wan, Yu-Hsin, Feng, Junli, Whaley, Rachael E., Singh, Suruchi, Boeckh, Michael, Cohen, Kristen W., McElrath, M. Juliana, Englund, Janet A., Chu, Helen Y., Pancera, Marie, McGuire, Andrew T., Stamatatos, Leonidas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.07.2020; Elsevier Limited
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Antibodies; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; B cells; B-Lymphocytes - immunology; Betacoronavirus - immunology; Binding; Binding Sites; Coronavirus Infections - immunology; Coronavirus Infections - prevention & control; Coronaviruses; COVID-19; Epitopes; Epitopes, B-Lymphocyte - immunology; Glycoproteins; Humans; Infections; Lymphocytes B; MERS; Monoclonal antibodies; Mutation; neutralization; Neutralizing; Pandemics; Pandemics - prevention & control; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - immunology; Pneumonia, Viral - prevention & control; Protein Binding; Proteins; receptor-binding domain; Receptors; Receptors, Virus - metabolism; SARS; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Somatic Hypermutation, Immunoglobulin - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; spike protein; Vaccines; Viral diseases; Viral Vaccines - immunology; Viruses; COVID-19; ACE2; SARS-CoV-2; neutralization; spike protein; receptor-binding domain; SARS; antibodies; B cells; MERS
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2020.06.001

Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease. 45 S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation with limited clonal expansion, and three bound the receptor-binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine design. [Display omitted] •Early B cell responses to SARS-CoV-2 spike protein are analyzed from a COVID-19 patient•Most antibodies target non-neutralizing epitopes outside the RBD•A potent neutralizing mAb blocks the interaction of the S protein with ACE2•Neutralizing antibodies are minimally mutated Seydoux et al. analyze B cell responses in a COVID-19 patient and find that SARS-CoV-2 infection expands diverse B cell clones against the viral spike glycoprotein (S). Two neutralizing antibodies were identified that bind S with high affinity despite being minimally mutated. Thus, vaccine-induced neutralizing antibody responses may require activation of specific naive B cells without requiring extensive somatic mutation.