Development of a Staph Aureus Vaccine

金黄色葡萄球菌疫苗的开发

• 批准号: 10699035
• 负责人: Stephen Jeffrey Dollery
• 金额: $ 29.64万
• 依托单位: BIOLOGICAL MIMETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699035
• 关键词: Abscess; Acinetobacter baumannii; Acute; Acute Disease; Animal Model; Antibiotic Resistance; Antibiotics; Antigenic Variation; Antigens; Antioxidants; Bacteremia; Bacteria; Bacterial Antibiotic Resistance; Cells; Cessation of life; Chikungunya virus; Chronic; Chronic Disease; Clinical Trials; Complex; Coupled; Data; Deceptive Imprinting; Deinococcus radiodurans; Development; Disease; Dose; Economic Burden; Endocarditis; Epitopes; Exposure to; Failure; Future; Generations; Goals; Health; Healthcare; Healthcare Systems; Human; Human poliovirus; Immune; Immunity; Implant; Incidence; Infection; Intensive Care; Investments; Learning; Legal patent; Linezolid; Manganese; Methicillin; Methods; Microbial Biofilms; Modeling; Nosocomial Infections; Operative Surgical Procedures; Osteomyelitis; Patients; Persons; Phase; Pneumonia; Polysaccharides; Positioning Attribute; Preparation; Preventive measure; Preventive vaccine; Protein Subunits; Reagent; Reporting; Resistance; Set protein; Skin Tissue; Small Business Innovation Research Grant; Soft Tissue Infections; Staphylococcal Vaccines; Staphylococcus aureus; Testing; Toxic effect; United States; Urinary tract infection; Vaccines; Vancomycin; Venezuelan Equine Encephalitis Virus; Viral Vaccines; Whole Cell Vaccine; bacterial resistance; cost; cross immunity; experimental study; fighting; implantable device; implantation; imprint; inorganic phosphate; insight; irradiation; lead candidate; medical implant; methicillin resistant Staphylococcus aureus; mimetics; mouse model; next generation; novel; preclinical study; preservation; prototype; radioresistant; resistant strain; response; technology development; vaccine candidate

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.

抽象的 尽管如此，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。 在用于预防措施的数十亿美元中，估计发生率有数百起 数千人，仅在美国每年就有数万人死于疾病。 金黄色葡萄球菌疫苗将对抗击抗生素耐药性的医疗保健产生巨大影响 在我们之前的研究中，我们使用了一种新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产生高水平的清除率。 采用锰-十肽-磷酸盐 (MDP) 复合物，该复合物改编自抗辐射材料 我们建议通过直接比较几种细菌来进一步开发这种方法。 已确定的候选疫苗和下一代改良版本将在扩大研究中进行。 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。 选定的“最佳”候选者还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 集）规避欺骗性免疫印记，这些实验应该让我们能够明确地报告哪些。 候选者在相关动物模型中被证明是最有效的，并使候选者做好交叉准备 随后进行保护、剂量和毒性研究。