Generation, characterization and epitope mapping of neutralizing and protective monoclonal antibodies against staphylococcal enterotoxin B induced lethal shock

摘要: T-cell stimulating activity of Staphylococcal enterotoxin B (SEB) is an important factor in the pathogenesis certain staphylococcal diseases including SEB mediated shock. one most potent superantigens known and treatment induced shock remains a challenge. We generated characterized murine monoclonal antibodies (mAbs) to mice. tested mAbs neutralize mitogenic effects vitro vivo with proliferation assays 2 models for lethal (SEBILS). Epitope mapping suggests that all these recognize conformational epitopes are destroyed by deleting C terminus protein. Further site-directed mutagenesis identified potential residues involved binding differ between Methicillin resistant sensitive Staphylococcus aureus strains. Only mAb 20B1 was effective as monotherapy treating SEBILS HLA DR3 transgenic mice, which exhibit enhanced sensitivity SEB. It noteworthy mAbs, 14G8 6D3 were not protective when given alone mice but their efficacy protection could be greatly co-administered simultaneously. Our data suggest combinations defined may constitute better strategy provide new insight development passive immunotherapy.