NEW LIPOSOME TECHNOLOGY FOR VACCINES

用于疫苗的新型脂质体技术

• 批准号: 3489721
• 负责人: DAVID H BING
• 金额: $ 5万
• 依托单位: CBR LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-15 至 1993-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3489721
• 关键词: amphiphilicity; antiserum; biological models; cellular immunity; chemical stability; dosage; hepatitis B antigens; hepatitis B virus group; hepatitis vaccine; humoral immunity; immunomodulators; laboratory mouse; liposomes; method development; phospholipids; radioimmunoassay

The long term goal of our project is to define the biochemical and immunological characteristics of a vaccine delivery system that will be stable to both environmental and biological effects, thus allowing for sustained and prolonged release of immunogens, maximal stimulation of the immune system, and protective immunity to pathogens. Liposomes prepared from phospholipids (PL) have been proposed to be a system that will enhance immunity to a wide variety of antigens, but they have not gained wide-use, presumably because of problems of cost and variable biochemical stability. We have data that suggests that a non-phospholipid liposome (NPL) made with a variety of single-tailed biodegradable amphiphiles solve these problems. Our hypothesis is that NPL will overcome the main disadvantage of PL's as carriers of antigens, namely lack of stability both in vitro and in vivo, but will have all of the previously documented advantages of PL in terms of delivery of immunogens and modulation of cells of the immune system. We are proposing to investigate in controlled studies in the mouse model, the immune system. We are proposing to investigate in controlled studies in the mouse model, the immune response to purified Hepatitis B (HB) antigens encapsulated in NPL. We will pursue 2 specific aims in this Phase I feasibility study to test: 1. Comparative studies on different chemical formulations of PL's and NPL's in terms of in vitro stability of NPL's. 2. The immunogenicity of HBsAg encapsulated in NPL's. Our studies are a prerequisite to Phase II studies that would test whether this system can be used for development of vaccines with extended stability that are effective in inducing protective long-term immunity to pathogens.

我们项目的长期目标是定义生化和 疫苗输送系统的免疫学特征 对环境和生物效应稳定，从而允许 持续和延长免疫原的释放，最大程度地刺激 免疫系统，以及对病原体的保护性免疫力。 脂质体制备 磷脂（PL）已被提议作为一个系统，将 增强对多种抗原的免疫力，但尚未获得 广泛使用，大概是因为成本和可变生化问题 稳定。 我们有数据表明非磷脂脂质体 (NPL) 由多种单尾可生物降解两亲物制成 解决这些问题。 我们的假设是不良贷款将克服主要问题 PL 作为抗原载体的缺点，即缺乏稳定性 体外和体内，但将具有所有先前记录的 PL 在免疫原递送和免疫调节方面的优势 免疫系统的细胞。 我们建议调查 小鼠模型免疫系统的对照研究。 我们是 提议在小鼠模型的对照研究中进行调查， 对封装在其中的纯化乙型肝炎 (HB) 抗原的免疫反应 不良贷款。 我们将在第一阶段可行性研究中追求两个具体目标 测试： 1. 不同化学配方的比较研究 PL 和 NPL 就 NPL 的体外稳定性而言。 2. 的 NPL 中封装的 HBsAg 的免疫原性。 我们的研究是一个 第二阶段研究的先决条件，该研究将测试该系统是否可以 用于开发具有延长稳定性的疫苗 有效诱导对病原体的长期保护性免疫力。