Scaffold vaccination for prevention of orthopedic device infection

<i>Staphylococcus aureus</i> is the leading cause of global bacterial mortality. While <i>S. aureus</i> can cause a variety of diseases, orthopedic device infections are particularly challenging due to the need for additional surgeries with associated morbidity. Conventional vaccine technology has failed to prevent <i>S. aureus</i> orthopedic device infection in animal models and clinical trials. In this study, injectable scaffold vaccines are presented as a modality to augment host immunity and mitigate orthopedic device infection. These scaffold vaccines increased cytokine production, antigen-specific cell-mediated immune responses, and humoral responses. When loaded with a pool of antigens collected via an engineered human opsonin, these scaffold vaccines decreased the bacterial burden against methicillin-susceptible and methicillin-resistant <i>S. aureus</i> (MRSA) strains in a murine model of orthopedic device infection. Scaffold vaccination was ~100× more effective in decreasing <i>S. aureus</i> burden compared to prior published immunotherapy attempts in murine models of orthopedic device infection. Scaffold vaccination was also effective when using a monovalent protein-based antigen. Scaffold vaccination is an alternative strategy to facilitate more robust immunity in scenarios where conventional bolus vaccines have not been effective.