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医院获得性感染的原型。尽管 在用于预防措施的数十亿美元中， 成千上万，仅在美国每年就有数万人死于疾病。预防性 疫苗抗S.金黄色葡萄球菌将对医疗保健对抗耐药性产生巨大影响， 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， 候选疫苗在严格的生物膜感染模型中导致高水平的清除。述的方法 利用锰-十肽-磷酸（MDP）复合物，该复合物已从抗辐射的 细菌，耐辐射球菌。我们建议通过直接比较几种方法来进一步发展这种方法。 在扩大研究中确定的候选疫苗和下一代改良版本。候选人将 在生物膜针植入和脓肿小鼠模型中测试刺激保护性免疫。向下- 选定的“最佳”候选人也将在S.金黄色葡萄球菌预暴露模型作为不同的免疫原（蛋白 套）规避欺骗性免疫印迹。这些实验应该让我们明确地报告， 候选人在相关动物模型中证明是最有效的，并将候选人定位为准备用于交叉试验。 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.