VLP-based Vaccines for Targeting Staphylococcus Aureus β-barrel Toxins

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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 virus-like particle (VLP)-based vaccine strategy to control SA secreted β-barrel pore-forming toxins. In models of skin infection, a vaccine based on this approach induces antibodies that prevent infection pathogenesis, spares host immune cells and limits disease. In this proposal, we aim to evaluate the preclinical potential of this vaccine strategy against a variety of SA β-barrel pore-forming toxins. We will determine vaccine immunogenicity in vivo, and efficacy in SA colonization. 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 SA infections.