ADHESIN BASED STAPHYLOCOCCAL IMMUNOTHERAPEUTICS

基于粘附素的葡萄球菌免疫治疗

• 批准号: 2777511
• 负责人: Joseph M. Patti
• 金额: $ 9.94万
• 依托单位: INHIBITEX, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2000-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2777511
• 关键词: Macaca mulatta; Staphylococcus aureus; adhesin; antibacterial agents; antigen antibody reaction; bacterial proteins; bacterial vaccines; blocking antibody; drug design /synthesis /production; drug resistance; endocarditis; enzyme linked immunosorbent assay; immunotherapy; laboratory rabbit; vaccine development

Staphylococcus aureus is a major cause of both nosocomial and community-acquired infections. Antibiotics have been the treatment of choice in the past; however there has been a dramatic increase in the number of antibiotic resistant S. aureus isolates. Thus, alternative prevention and treatment strategies are desperately needed. Microbial adhesion is the first step in the pathogenic process of bacterial infections and therefore is an attractive target for novel immunotherapeutics. S. aureus colonizes the host by attaching to host tissues or serum conditioned implanted biomaterials through a family of adhesins called MSCRAMM that recognize and specifically bind to distinct components in the host's extracellular matrix. Preliminary results generated by Inhibitex, Inc., has demonstrated that MSCRAMM specific high affinity blocking antibodies can be generated and that these antibodies protect animals against infection. The goal of this proposal is to design and produce a prototype MSCRAMM-based multi-component vaccine, characterize the immune response of animals immunized with the vaccine, and test the ability of the vaccine to protect animals against S. aureus infections. PROPOSED COMMERCIAL APPLICATIONS: The need for novel approaches to fight S. aureus infections are necessary, especially in the light of the increased emergence of antibiotic resistant organisms. MSCRAMMs provide an excellent target for intervention since they participate in the first step in the development of most infections. The prophylactic extensions of this technology are extremely appealing given the escalating cost of health care.

金黄色葡萄球菌是医院和社区获得感染的主要原因。抗生素过去一直是首选的治疗方法。然而，抗生素抗生素链球菌分离株的数量显着增加。因此，迫切需要替代预防和治疗策略。微生物粘附是细菌感染致病过程中的第一步，因此是新型免疫治疗剂的有吸引力的靶标。金黄色葡萄球菌通过通过称为MSCRAMM的粘附蛋白连接到宿主组织或血清条件植入生物材料的宿主通过，并专门结合了宿主细胞外基质中的不同成分。 Inhipitex，Inc。产生的初步结果表明，可以产生MSCRAMM特异性高亲和力阻断抗体，并且这些抗体可保护动物免受感染。 该提案的目的是设计和生产原型MSCRAMM的多组分疫苗，表征用疫苗免疫的动物的免疫反应，并测试疫苗保护动物免受金黄色葡萄球菌感染的能力。拟议的商业应用：需要新颖的方法来对抗金黄色葡萄球菌感染，尤其是鉴于抗生素耐药生物的出现增加。 MSCramms为干预提供了一个绝佳的目标，因为他们参与了大多数感染的第一步。鉴于医疗保健的成本不断上升，该技术的预防性扩展非常有吸引力。