VLP-based vaccine induces immune control of Staphylococcus aureus virulence regulation

摘要: Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) mounting antibiotic resistance requires innovative treatment strategies. S. uses secreted cyclic autoinducing peptides (AIPs) accessory gene regulator (agr) operon to coordinate expression virulence factors required for invasive infection. Of four agr alleles (agr types I-IV corresponding AIPs1-4), type I isolates are most frequently associated with Cyclization via a thiolactone bond essential AIP function; therefore, recognition form AIP1 may be necessary antibody-mediated neutralization. However, small sizes AIPs labile have hindered vaccine development. To overcome this, we used virus-like particle (VLP) platform (PP7) conformationally-restricted presentation modified amino acid sequence (AIP1S). Vaccination PP7-AIP1S elicited AIP1-specific antibodies limited agr-activation in vivo. Importantly, murine SSTI challenge model highly virulent isolate, vaccination reduced pathogenesis increased bacterial clearance compared controls, demonstrating efficacy. Given contribution MRSA human disease, targeting AIP1-regulated could major clinical impact fight against resistance.