Immunogenicity and pharmacokinetics of short, proline-rich antimicrobial peptides

Abstract

Aim: The potential of proline-rich antimicrobial peptides (PrAMPs) to treat multidrug-resistant Gram-negative pathogens has been intensively investigated. They are efficacious at low doses in infection models and well tolerated in healthy mice at high doses. Methods & results: PrAMPs Onc72 and Api88 were nonimmunogenic in mice unless conjugated to a carrier protein. Monoclonal IgG1/IgG2b antibodies produced by hybridoma cells were mapped to different Onc72 regions and combined in a sandwich-ELISA in a pharmacokinetic study. Onc72 was detected at concentrations up to 32 µg/ml in murine blood after administering 20 mg/kg and reached several organs within 10 min. Conclusion: Both PrAMPs were not immunogenic and Onc72 concentrations in blood were well above the minimal inhibitory concentrations for Enterobacteriaceae further confirming their potential as novel antibiotics.