Harnessing antifungal immunity in pursuit of a Staphylococcus aureus vaccine strategy.

Staphylococcus aureus(S.aureus) is one of the most common bacterial infections worldwide, and antibiotic resistant strains such as Methicillin-ResistantS.aureus(MRSA) are a major threat and burden to public health. MRSA not only infects immunocompromised patients but also healthy individuals and has rapidly spread from the healthcare setting to the outside community. However, all vaccines tested in clinical trials to date have failed. Immunocompromised individuals such as patients with HIV or decreased levels of CD4(+)T cells are highly susceptible toS.aureusinfections, and they are also at increased risk of developing fungal infections. We therefore wondered whether stimulation of antifungal immunity might promote the type of immune responses needed for effective host defense againstS.aureus. Here we show that vaccination of mice with a fungal beta-glucan particle (GP) loaded withS.aureusantigens provides protective immunity toS.aureus. We generated glucan particles loaded with the fourS.aureusproteins ClfA, IsdA, MntC, and SdrE, creating the 4X-SA-GP vaccine. Vaccination of mice with three doses of 4X-SA-GP promoted protection in a systemic model ofS.aureusinfection with a significant reduction in the bacterial burden in the spleen and kidneys. 4X-SA-GP vaccination induced antigen-specific Th1 and Th17 CD4(+)T cell and antibody responses and provided long-term protection. This work suggests that the GP vaccine system has potential as a novel approach to developing vaccines forS.aureus. Author summary Staphylococcus aureus(S.aureus) is a serious burden to public health as it is a leading cause of antibiotic-resistant infections worldwide. Vaccines aimed at targetingS.aureushave failed in clinical trials, and the reason for this lack of success remains unclear. As this pathogen continues to rapidly spread on a global scale, it is vital that new approaches toS.aureusvaccination are developed. In this study, we show that activation of antifungal immunity with a beta-glucan particle vaccine can be harnessed to direct protection againstS.aureussystemic infections in mice. This work broadens the use of the beta-glucan particle vaccine system for potential use as a much-needed vaccine targetingS.aureus.