Vaccine-mediated control of bacterial virulence regulation and infection

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PROJECT SUMMARY: Staphylococcus aureus (SA), including methicillin-resistant (MRSA), is the most common cause of skin and soft tissue infection (SSTI) in the US. SA causes recurrent infections, particularly in highly susceptible patient populations with reduced immune function. To date, no vaccine to prevent SA infection has succeeded in human trials. Meanwhile, the need for a vaccine continues to escalate, as does the ability of this pathogen to acquire antibiotic resistance. We have developed a novel vaccine to control regulation of SA virulence factor production. In models of skin infection, this vaccine induces antibodies that prevent activation of this regulator system and protect against invasive infection. In this proposal, we aim to evaluate the preclinical potential of this vaccine strategy. We will determine vaccine efficacy in multiple models of SA infection as well as models of reduced immune function. Our results could lay the groundwork for development of an efficacious vaccine to prevent SA infection and limit pathogenesis. This vaccine could significantly improve the health of patients who suffer from invasive SA infections.