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Human monoclonal antibodies that target the SFTSV glycoprotein Gn head from four neutralizing epitope groups - PubMed

4 hours ago
  • #therapeutic candidates
  • #neutralizing antibodies
  • #SFTSV
  • Isolated 84 human monoclonal antibodies (mAbs) from SFTS survivors targeting SFTSV glycoproteins Gn and Gc.
  • Gn-specific mAbs showed broader and more potent neutralization than Gc-specific mAbs.
  • Classified Gn-head mAbs into eight epitope groups using yeast display deep mutational scanning, with four groups (IA, ID, IIIA, IIIB) conferring neutralization.
  • Identified mAbs BD70-4003 (group IA) and BD70-4017 (group IIIA) for broad neutralization and 100% protection in a lethal mouse model.
  • Used cryo-EM structural analysis to validate epitope residues and reveal binding interfaces of mAbs with Gn head.
  • Delineated SFTSV Gn antigenic landscape and established DMS with structural validation as a framework for bunyavirus antibody discovery.