Generating protective immunity to Staphylococcus aureus

摘要 S.金黄色葡萄球菌在世界范围内引起猖獗的感染，并对公众健康构成重大威胁。随着 抗生素耐药性，已经有一个主要的推动发展一个有效的疫苗对S。金黄色。然而，在这方面， 尽管几十年的努力和未知的原因，所有S。在临床试验中测试的金黄色葡萄球菌疫苗已经失败。 我们在小鼠模型中的初步工作表明，使用正确的佐剂可能是开发一种免疫抑制剂的关键。 成功的疫苗我们发现，β-葡聚糖（来自真菌细胞壁）和刺激性 S.金黄色葡萄球菌协同作用，提供了强大的Th17介导的保护，以S。金黄色葡萄球菌再感染在这里， 我们将研究由这些佐剂刺激的免疫保护的潜在机制。我们将探讨 分子机制和参数决定的效力和保护的持续时间。我们将进一步 研究在人源化的S.金黄色葡萄球菌感染。这项研究将 提供了一个更好的基本了解如何提高保护性免疫反应，以S。金黄色罐头 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.