BLOCKING STD PATHOGEN ENTRY WITH MUCOSAL ANTIBODIES

用粘膜抗体阻断性病病原体进入

• 批准号: 6500706
• 负责人: Kevin John Whaley
• 金额: $ 18.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6500706
• 关键词: Chlamydiaceae; Neisseria gonorrhoeae; antibacterial agents; antiviral agents; biotechnology; disease /disorder model; genetically modified animals; herpes simplex virus 2; human papillomavirus; laboratory mouse; laboratory rabbit; monoclonal antibody; mucosal immunity; pharmacokinetics; sexually transmitted diseases; topical drug application; vagina

Many vaginal microbicides being evaluated for the prevention of sexually transmitted diseases (STDs) have broad-spectrum actions that are not limited to pathogens, e.g. detergents may disrupt epithelial integrity: In contrast, antibodies are microbicides that are highly specific, yet, by working in combination can achieve broad spectrum protection without injuring healthy tissues or commensals. The specificity of antibodies together with their versatility and diversity make them leading candidates (as well as tools) for developing specific microbicides that can block pathogen entry across the vaginal mucosa. Biotechnology products are now being produced in plants both to achieve low cost and high capacity production, and the first specific aim is to determine the pharmacokinetics in the mouse and rabbit vagina of a human antibody to HSV2 produced transgentically in corn as a "plantibody". After determining the most efficacious targets using existing mouse antibodies in mouse models, the next aims are to generate protective human monoclonal antibodies in mouse models, the next two aims are to generate protective human monoclonal antibodies to HPV 16 by phage display and to cell-associated HIV, chlamydia and gonorrhea in transgenic mice. These human monoclonal antibodies will be evaluated in vitro and in STD/mouse models for protective efficacy. Since antibodies may help create a vaginal environment in which protective commensals can flourish, the final aim is to test the concept that typically applied antibodies can specifically reduce a potentially harmful vaginal commensal in mice. A combination of these human monoclonal antibodies will form the basis for the development of a broad-spectrum yet specific microbicide to prevent sexually transmitted diseases.

评估许多阴道微生物的预防性传播疾病（STD）具有不限于病原体的广谱作用，例如清洁剂可能会破坏上皮完整性：相反，抗体是高度特异性的杀菌剂，但是，通过组合工作可以实现广泛的保护，而无需伤害健康的组织或共生。抗体的特异性以及其多功能性和多样性使它们成为开发特定菌心的领先候选者（以及工具），这些杀菌剂可以阻止阴道粘膜的病原体进入。现在正在植物中生产生物技术产品，以实现低成本和高容量的产生，第一个具体目的是确定人类抗体的小鼠和兔阴道中的药代动力学对HSV2的HSV2在玉米中以“植物性植物”的形式传播。在使用鼠标模型中使用现有的小鼠抗体确定了最有效的靶标之后，下一个目标是在鼠标模型中生成保护性人类单克隆抗体，接下来的两个目的是通过噬菌体显示和与细胞相关的HIV，chlamydia和Transerorneice in phage Esplays生成保护性的人类单克隆抗体。这些人类单克隆抗体将在体外和性病/小鼠模型中评估以进行保护效果。由于抗体可能有助于创造一种阴道环境，在这种环境中，保护性共生可以蓬勃发展，因此最终的目的是测试通常施用的抗体可以特异性地减少小鼠中潜在有害的阴道分子的概念。这些人类单克隆抗体的结合将构成开发广谱但特定的菌心以防止性传播疾病的基础。