Therapeutic anti-glycan antibodies against antibiotic resistant <i>Staphylococcus aureus</i>

Abstract Antibiotic resistance threatens clinical control of bacterial infections while the genetic adaptability microbes continues to outpace small-molecule development. The combinatorial diversity antibodies offers a solution this problem. However, under normal circumstances polymeric glycans surfaces avoid adaptive recognition by not binding MHC molecules. Thus, they are T cell independent antigens and targeted only low affinity IgM responses. Glycoconjugate vaccines have been developed provide bystander help overcome limitation but failed elicit protective responses against antibiotic resistant Staphylococcus aureus in trials. To address limitations current conjugate vaccine approaches, we optimized anti-glycan B through three convergent prongs: exploiting cognate help, using cell-centric adjuvant, synthetic minimal glycans. This prototype next generation was used produce nanomolar proof-of-concept studies. Focusing on glycan targets wall capsule selected monoclonal antibodies. These were characterized structurally, biophysically, sequencing confirm high affinity, maturation, specificity towards intended targets. potential therapeutic benefits currently being tested preclinical mouse models: skin, lung, systemic infection, passive active immunization. Preliminary studies shown efficacy both preventative interventional model for some these Kenna Nagy supported by: NIH TL1TR002551 For project P.I. Luc Teyton U01 AI160338, R01 AI139748