S. aureus causes rampant infection worldwide and poses a significant threat to public health. With the spread of antibiotic resistance, there has been a major push to develop an effective vaccine against S. aureus. However, despite decades of effort and for unknown reasons, all S. aureus vaccines tested in clinical trials have failed. Our preliminary work in mouse models suggests that use of the right adjuvants could be the key to developing a successful vaccine. We showed that a combination of ?-glucan (derived from fungal cell walls) and stimulatory molecules from S. aureus synergize to provide robust Th17-mediated protection to S. aureus reinfection. Here, we will study mechanisms underlying immune protection stimulated by these adjuvants. We will explore the molecular mechanisms and parameters that determine the efficacy and duration of protection. We will further investigate the efficacy of the protection in a humanized mouse model of S. aureus infection. The study will provide a better fundamental understanding of how an improved protective immune response to S. aureus can be induced.
An effective vaccine is the ultimate goal in the war against S. aureus, which in recent years has become a major public health problem due to antibiotic resistance. All vaccines tested in clinical trials thus far have failed. Our data suggest that a solution may lie in understanding the underlying basic mechanisms of adjuvant efficacy. Here we propose a mechanistic study of how and why a fungal cell wall-derived adjuvant promotes robust and long lasting protection against S. aureus.
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