Development of a Staph Aureus Vaccine

摘要 耐甲氧西林金黄色葡萄球菌通常被认为是典型的医院获得性感染。尽管 在花费在预防措施上的数十亿美元中，对发病率的估计有数百 仅在美国，每年就有数以万计的人死于疾病。预防用药 针对金黄色葡萄球菌的疫苗将在对抗抗生素耐药性的医疗斗争中产生巨大影响 菌株。在我们以前的研究中，我们使用了一种新的方法来产生下一代全细胞葡萄球菌 在严格的生物被膜感染模型中，导致高水平清除的候选疫苗。方法 使用了一种锰-十肽-磷酸(MDP)络合物，它是从抗辐射的 细菌，耐辐射葡萄球菌。我们建议通过直接比较几个 在扩大的研究中确定的候选疫苗和下一代修改版本。候选人将 在生物膜针植入和脓肿小鼠模型中进行刺激保护性免疫的测试。向下- 选定的最佳候选者也将在金黄色葡萄球菌预暴露模型中作为不同的免疫原(蛋白质)进行测试 套装)绕过欺骗性免疫印记。这些实验应该可以让我们明确地报告 候选人在相关动物模型中被证明是最有效的，并将候选人定位为准备杂交- 随后进行保护、剂量和毒性研究。

Abstract Methicillin-resistant Staphylococcus aureus is often considered the prototype hospital-acquired infection. In spite of the billions of dollars spent on preventive measures, estimates of the incidence are in the hundreds of thousands, with tens of thousands of people per year succumbing to disease in the USA alone. Prophylactic vaccines against S. aureus would have an enormous impact in the healthcare fight against antibiotic-resistant strains. In our previous studies, we used a novel method to generate next-generation whole-cell Staphylococcus vaccine candidates that resulted in high levels of clearance in a stringent biofilm model of infection. The method utilizes a manganese-decapeptide-phosphate (MDP) complex that has been adapted from the radiation-resistant bacterium, Deinococcus radiodurans. We propose to further develop this approach by directly comparing several of the identified vaccine candidates and next-generation modified versions in expanded studies. Candidates will be tested for stimulating protective immunity in biofilm pin implantation and abscess mouse models. Down- selected “best” candidates will also be tested in a S. aureus preexposure model as different immunogens (protein sets) circumvent deceptive immune imprinting. These experiments should allow us to categorically report which candidate proves the most efficacious in relevant animal models, and position a candidate ready for cross- protection, dosing, and toxicity studies to follow.