Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants

• Published in: Science (American Association for the Advancement of Science) Vol. 373; no. 6556
• Main Authors: Wang, Lingshu, Zhou, Tongqing, Zhang, Yi, Yang, Eun Sung, Schramm, Chaim A., Shi, Wei, Pegu, Amarendra, Oloniniyi, Olamide K., Henry, Amy R., Darko, Samuel, Narpala, Sandeep R., Hatcher, Christian, Martinez, David R., Tsybovsky, Yaroslav, Phung, Emily, Abiona, Olubukola M., Antia, Avan, Cale, Evan M., Chang, Lauren A., Choe, Misook, Corbett, Kizzmekia S., Davis, Rachel L., DiPiazza, Anthony T., Gordon, Ingelise J., Hait, Sabrina Helmold, Hermanus, Tandile, Kgagudi, Prudence, Laboune, Farida, Leung, Kwanyee, Liu, Tracy, Mason, Rosemarie D., Nazzari, Alexandra F., Novik, Laura, O’Connell, Sarah, O’Dell, Sijy, Olia, Adam S., Schmidt, Stephen D., Stephens, Tyler, Stringham, Christopher D., Talana, Chloe Adrienna, Teng, I-Ting, Wagner, Danielle A., Widge, Alicia T., Zhang, Baoshan, Roederer, Mario, Ledgerwood, Julie E., Ruckwardt, Tracy J., Gaudinski, Martin R., Moore, Penny L., Doria-Rose, Nicole A., Baric, Ralph S., Graham, Barney S., McDermott, Adrian B., Douek, Daniel C., Kwong, Peter D., Mascola, John R., Sullivan, Nancy J., Misasi, John
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 13.08.2021; American Association for the Advancement of Science
• Subjects: ACE2; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - antagonists & inhibitors; Angiotensin-Converting Enzyme 2 - metabolism; Antibodies; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - metabolism; Antibodies, Viral - chemistry; Antibodies, Viral - immunology; Antibodies, Viral - metabolism; Antibody Affinity; Antigen-Antibody Reactions; Biochem; Coronavirus; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - virology; Donors; Humans; Immune Evasion; Immunoglobulin Fab Fragments - immunology; Immunoglobulin Fab Fragments - metabolism; Immunology; Mutation; Neutralization; Neutralization Tests; Outbreaks; Pandemics; Protein Domains; Proteins; Receptors, Coronavirus - antagonists & inhibitors; Receptors, Coronavirus - metabolism; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Vaccines; Viruses
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abh1766

Our key defense against the COVID-19 pandemic is neutralizing antibodies against the SARS-CoV-2 virus elicited by natural infection or vaccination. Recent emerging viral variants have raised concern because of their potential to escape antibody neutralization. Wang et al . identified four antibodies from early-outbreak convalescent donors that are potent against 23 variants, including variants of concern, and characterized their binding to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yuan et al . examined the impact of emerging mutations in the receptor-binding domain of the spike protein on binding to the host receptor ACE2 and to a range of antibodies. These studies may be helpful for developing more broadly effective vaccines and therapeutic antibodies. —VV Potently neutralizing antibodies from convalescent donors from the first wave of SARS-CoV-2 neutralize recent variants of concern. The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain–targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC 50 ) 0.3 to 11.1 nanograms per milliliter; IC 80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.