biostudies-literatureSheward DJNIAID NIH HHS101577https://www.ebi.ac.uk/biostudies/studies/S-EPMC11228396biostudies-literatureUnknown5(6)Descendants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant now account for almost all SARS-CoV-2 infections. The Omicron variant and its sublineages have spike glycoproteins that are highly diverged from the pandemic founder and first-generation vaccine strain, resulting in significant evasion from monoclonal antibody therapeutics and vaccines. Understanding how commonly elicited antibodies can broaden to cross-neutralize escape variants is crucial. We isolate IGHV3-53, using "public" monoclonal antibodies (mAbs) from an individual 7 months post infection with the ancestral virus and identify antibodies that exhibit potent and broad cross-neutralization, extending to the BA.1, BA.2, and BA.4/BA.5 sublineages of Omicron. Deep mutational scanning reveals Cell reports. MedicineStructural basis of broad SARS-CoV-2 cross-neutralization by affinity-matured public antibodies.PMC11228396R01 AI141707Kim CPeacock TPDopico XCGreaney AJLee JSheward DJCorcoran MHallberg BMKim SMurrell BDosenovic PBloom JDDas HPushparaj PAlbert JHyllner EDyrdak RHanke LMcInerney GMKarlsson Hedestam GBfalseStructural basis of broad SARS-CoV-2 cross-neutralization by affinity-matured public antibodies.Descendants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant now account for almost all SARS-CoV-2 infections. The Omicron variant and its sublineages have spike glycoproteins that are highly diverged from the pandemic founder and first-generation vaccine strain, resulting in significant evasion from monoclonal antibody therapeutics and vaccines. Understanding how commonly elicited antibodies can broaden to cross-neutralize escape variants is crucial. We isolate IGHV3-53, using "public" monoclonal antibodies (mAbs) from an individual 7 months post infection with the ancestral virus and identify antibodies that exhibit potent and broad cross-neutralization, extending to the BA.1, BA.2, and BA.4/BA.5 sublineages of Omicron. Deep mutational scanning reveals 2024-01-01T00:00:00Z2024 Jun2026-06-01T07:37:28.23Z2025-04-04T11:25:08.643ZS-EPMC112283963876179910.1016/j.xcrm.2024.101577