biostudies-literatureGruell HDeutsches Zentrum für InfektionsforschungDeutsche ForschungsgemeinschaftUniversität zu KölnBMBF BonnBundesinstitut für Arzneimittel und Medizinprodukte1231-1241.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC9260412biostudies-literatureUnknown30(9)SARS-CoV-2 neutralizing antibodies play a critical role in COVID-19 prevention and treatment but are challenged by viral evolution and the emergence of novel escape variants. Importantly, the recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. By determining polyclonal serum activity of 50 convalescent or vaccinated individuals against BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5, we reveal a further reduction in BA.4/5 susceptibility to vaccinee sera. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. Antigenic distance and/or higher resistance may therefore favor immune-escape-mediated BA.4/5 expansion after the first Omicron wave. Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Our study provides a detailed understanding of Omicron-sublineage antibody escape that can inform on effective strategies against COVID-19.Cell host & microbeSARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns.PMC9260412CRC1310V-2021.3/1503_68403/2021–202201KX2021Gruell HMunn FTober-Lau PJanicki HKorenkov MKlein FKreer CKurth FVanshylla KSchommers PAugustin MZehner MSander LEfalseSARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns.SARS-CoV-2 neutralizing antibodies play a critical role in COVID-19 prevention and treatment but are challenged by viral evolution and the emergence of novel escape variants. Importantly, the recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. By determining polyclonal serum activity of 50 convalescent or vaccinated individuals against BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5, we reveal a further reduction in BA.4/5 susceptibility to vaccinee sera. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. Antigenic distance and/or higher resistance may therefore favor immune-escape-mediated BA.4/5 expansion after the first Omicron wave. Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Our study provides a detailed understanding of Omicron-sublineage antibody escape that can inform on effective strategies against COVID-19.2022-01-01T00:00:00Z2022 Sep2026-05-28T00:37:37.963Z2025-04-22T16:36:10.221ZS-EPMC92604123592183610.1016/j.chom.2022.07.002