biostudies-literatureHastie KMSwiss National Science FoundationNIAID NIH HHS472-478https://www.ebi.ac.uk/biostudies/studies/S-EPMC9302186biostudies-literatureUnknown374(6566)Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.Science (New York, N.Y.)Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.PMC9302186U19 AI142790195680R01 AI147870T32 AI125179Sato AKLan FPeters BLujan Hernandez AGLu YIngraham JRikhtegaran Tehrani ZHastie KMShen BZhang QLang GBedinger DOlmedillas EHuang KASajadi MMLi HEnriquez AParekh DSanders RWHui SHorn GQAldon YShaffer KYuan TZLeung CLCobb RRLi KSnitselaar JLBuck THo DDTan YFederman RSSaphire EOKim CLee SLiu JCoVIC-DB team1Glanville JAbraha MRabbitts THDennison SMYu JKim MDiaz Avalos RTomic MTStamatatos LYoussef SJiang WZyla DAracic SYu XGermann TFeeney EAli HKim HMHariharan CRayaprolu VZandonatti MSeo JFernandez JMMcGuire ATKong CSchendel SLKellam Pvan Gils MJPalser ALGreen RMacCamy AMann CKrebs SJTomaras GDGrigoryan GSchweizer LYin JfalseDefining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.2021-01-01T00:00:00Z2021 Oct2026-05-27T22:50:17.767Z2026-04-08T01:56:23.712ZS-EPMC93021863455482610.1126/science.abh2315