biostudies-literatureUnknownGieselmann LEuropean Research CouncilNIAID NIH HHSGates FoundationAdministration of HIV-1 neutralizing antibodies can suppress viremia and prevent infection <i>in vivo</i>. However, clinical use is challenged by broad envelope sequence diversity and rapid emergence of viral escape^1-9. Here, we performed single B cell profiling of 32 top HIV-1 elite neutralizers to identify broadly neutralizing antibodies (bNAbs) with highest potency and breadth for clinical application. From 831 expressed monoclonal antibodies, we identified 04_A06, a new V_H1-2-encoded CD4 binding site bNAb with remarkable breadth and potency against extended multiclade pseudovirus panels (GeoMean IC₅₀ = 0.059 μg/ml, breadth = 98.5%, 332 virus strains). Moreover, 04_A06 was not susceptible to classic viral CD4bs escape variants and maintained full viral sbioRxiv : the preprint server for biology2025.08.27.672638https://www.ebi.ac.uk/biostudies/studies/S-EPMC12407976biostudies-literatureProfiling a large HIV-1 elite neutralizer cohort reveals remarkable CD4bs bNAb for HIV-1 prevention and therapy.PMC12407976U01 AI169385R01 AI140891724208P01 AI100148INV-036842INV-002143U54 AI170856West APGiovannoni FRohde MHoelscher MZhang LHavenar-Daughton CErcanoglu MSKroidl ABjorkman PJCorti DLehmann CBenigni FAdhikari AAmbada GEGilbert PBDeLaitsch ATStumpf RKnufer JGristick HBReichwein MLMkhize NNStefanutti EKaldine HWorczinski JDoria-Rose NAMoore PLMora TNtinginya NEGeldmacher CDuerr RSchommers PSeaman MSGieselmann LNanfack AJRadford CGruell HWolf TWilliam WAhmadov EMaganga LWalczak AMMomot AMazzolini AKlein FBloom JDKreer CHuang YDeshpande SBhebhe SfalseProfiling a large HIV-1 elite neutralizer cohort reveals remarkable CD4bs bNAb for HIV-1 prevention and therapy.Administration of HIV-1 neutralizing antibodies can suppress viremia and prevent infection <i>in vivo</i>. However, clinical use is challenged by broad envelope sequence diversity and rapid emergence of viral escape^1-9. Here, we performed single B cell profiling of 32 top HIV-1 elite neutralizers to identify broadly neutralizing antibodies (bNAbs) with highest potency and breadth for clinical application. From 831 expressed monoclonal antibodies, we identified 04_A06, a new V_H1-2-encoded CD4 binding site bNAb with remarkable breadth and potency against extended multiclade pseudovirus panels (GeoMean IC₅₀ = 0.059 μg/ml, breadth = 98.5%, 332 virus strains). Moreover, 04_A06 was not susceptible to classic viral CD4bs escape variants and maintained full viral s2025-01-01T00:00:00Z2025 Aug2026-04-08T19:48:33.213Z2026-04-08T14:33:21.099ZS-EPMC124079764090975210.1101/2025.08.27.672638