Generation and Application of Mutant Superantigens for Vaccine against Staphylococcus Aureus Infections
Fortin, Ye Ji Lee
AdvisorSeo, Keun Seok
CommitteePruett, Stephen B.
Pinchuk, Lesya M.
Staphylococcus aureus (S. aureus) is a frequent cause of infections and sepsis in animals and humans worldwide. Staphylococcal enterotoxins and toxic shock syndrome toxin-1 are bacterial superantigens (SAgs) produced by S. aureus that simultaneously bind to T cell receptor (TCR) and the major histocompatibility complex (MHC) class II, leading to extensive T cell stimulation, release of cytokines, consequently resulting in toxic shock and immunosuppression. In this study, we generated mutant SAgs by introducing alanine substitution at residues involved in interaction with MHC class II and TCR binding and demonstrated attenuation of toxicity in vitro and in vivo. An immunization with mutant SAgs elicits production of neutralizing antibodies against wild type SAgs and protected animals from S. aureus peritonitis at a lethal dose. These results suggest that mutant SAgs will be useful to develop a novel vaccine against S. aureus infections.