Generating protective immunity to Staphylococcus aureus

摘要 金黄色葡萄球菌在全球范围内造成猖獗的感染，并对公众健康构成重大威胁。随着病毒的传播 在抗生素耐药性方面，人们一直在大力推动开发一种有效的金黄色葡萄球菌疫苗。然而， 尽管几十年的努力和未知的原因，所有在临床试验中测试的金黄色葡萄球菌疫苗都失败了。 我们在小鼠模型上的初步工作表明，使用正确的佐剂可能是开发出 成功的疫苗。我们证明了β-葡聚糖(来自真菌细胞壁)和刺激性 来自金黄色葡萄球菌的分子协同作用，为金黄色葡萄球菌的再感染提供强大的Th17介导的保护。这里, 我们将研究这些佐剂刺激免疫保护的潜在机制。我们将探索 决定保护效果和持续时间的分子机制和参数。我们将进一步 在人源化的金黄色葡萄球菌感染小鼠模型中，研究该保护措施的有效性。这项研究将 更好地从根本上理解对金黄色葡萄球菌的保护性免疫反应是如何 被诱导。

ABSTRACT 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 β-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.