Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

• Published in: Science (American Association for the Advancement of Science) Vol. 373; no. 6556; pp. 818 - 823
• Main Authors: Yuan, Meng, Huang, Deli, Lee, Chang-Chun D., Wu, Nicholas C., Jackson, Abigail M., Zhu, Xueyong, Liu, Hejun, Peng, Linghang, van Gils, Marit J., Sanders, Rogier W., Burton, Dennis R., Reincke, S. Momsen, Prüss, Harald, Kreye, Jakob, Nemazee, David, Ward, Andrew B., Wilson, Ian A.
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 13.08.2021; AAAS; American Association for the Advancement of Science
• Subjects: 60 APPLIED LIFE SCIENCES; ACE2; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - metabolism; Antibodies, Viral - immunology; Antibodies, Viral - metabolism; Antigenic drift; Antigenic Variation; Antigens, Viral - chemistry; Antigens, Viral - genetics; Antigens, Viral - immunology; Antigens, Viral - metabolism; BASIC BIOLOGICAL SCIENCES; Binding Sites; Binding Sites, Antibody; Biochem; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - virology; COVID-19 vaccines; Epitopes; Humans; Immune Evasion; Microbio; Mutation; Neutralization; Pandemics; Protein Binding; Protein Domains; Proteins; Receptors, Coronavirus - metabolism; SARS-CoV-2 - chemistry; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Structure-function relationships; Vaccines
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abh1139

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. Neutralizing antibodies (nAbs) elicited against the receptor binding site (RBS) of the spike protein of wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are generally less effective against recent variants of concern. RBS residues Glu 484 , Lys 417 , and Asn 501 are mutated in variants first described in South Africa (B.1.351) and Brazil (P.1). We analyzed their effects on angiotensin-converting enzyme 2 binding, as well as the effects of two of these mutations (K417N and E484K) on nAbs isolated from COVID-19 patients. Binding and neutralization of the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2), which can both bind the RBS in alternative binding modes, are abrogated by K417N, E484K, or both. These effects can be structurally explained by their extensive interactions with RBS nAbs. However, nAbs to the more conserved, cross-neutralizing CR3022 and S309 sites were largely unaffected. The results have implications for next-generation vaccines and antibody therapies.