IMMUNE ENHANCEMENT OF POLIOVIRUS ANTIGENICITY

脊髓灰质炎病毒抗原性的免疫增强

• 批准号: 3546705
• 负责人: Marie Chow
• 金额: $ 22.83万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1990-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3546705
• 关键词: T lymphocyte; antibody formation; antiserum; antiviral antibody; disease /disorder model; immunization; laboratory mouse; leukocyte activation /transformation; poliovirus; polymers; tissue /cell culture; tyrosine; viral vaccines; virus antigen; virus envelope; virus infection mechanism

The aim of the proposed research is to test the feasibility of enhancing the immune response of viral antigens by microencapsulation in slow release biopolymers. Because the immunogenicity of poliovirus viral antigens has been extensively characterized, the poliovirus subunit antigens provide an excellent model system with which to test the ability of controlled release devices to enhance the immunogenicity of these antigens. Specifically, a combination of chemical, biochemical and immunological approaches are proposed to study the effectiveness of microencapsulated poliovirus antigens to induce antibody responses and the feasibility of using biocompatable polymers to control release and presentation of viral antigens during immunization and potentially increase the induction of neutralizing antibodies. To achieve these goals: 1. Individual poliovirus antigens will be encapsulated into several different hypdrophobic degradable and non- degradable (FDA approved) polymers. The antigen- imbedded polymers will be characterized physically and the release profiles determined in vitro and in mice. 2. The antibody response induced in mice by the microencapsulated poliovirus antigens will be characterized. The immune response induced by the microencapsulated antigens will be characterized and compared with response induced by antigen-Freunds adjuvant emulsions or with antigen-alum adjuvant mixtures. 3. The molecular mechanisms of the phenomenon of "wetting" will be studied. Methods will be sought to overcome this often encountered problem with controlled release of biologically active proteins. 4. The ability of the microencapsulated antigens to elicit and stimulate T cell responses will be examined. This response will be compared to that induced by the intact virion. Successful vaccines must be able to induce a immune response which is sufficient to protect the host from the adverse consequences of viral infection. The experiments described here are designed to contribute to the development of methods and techniques that potentially will increase the general utility of viral and subviral antigens as successful vaccine antigens.

该研究的目的是测试 增强病毒抗原的免疫应答， 缓释生物聚合物中的微囊化。 因为 脊髓灰质炎病毒抗原免疫原性已经被广泛地 特征在于，脊髓灰质炎病毒亚单位抗原提供了优异的免疫学特性。 模型系统，用于测试控释能力 增强这些抗原的免疫原性的装置。 具体地说，化学、生物化学和 提出了免疫学方法来研究其有效性 微囊化脊髓灰质炎病毒抗原诱导抗体 反应和使用生物相容性聚合物的可行性， 控制释放和呈递病毒抗原 免疫接种，并可能增加诱导 中和抗体 为实现这些目标： 1.单个脊髓灰质炎病毒抗原将被封装在 几种不同的疏水可降解和非疏水 可降解（FDA批准）聚合物。 抗原- 嵌入的聚合物将在物理上表征， 在体外和小鼠中测定的释放曲线。 2.小鼠中由抗人IgG抗体诱导的抗体应答 将表征微囊化脊髓灰质炎病毒抗原。 微囊化免疫球蛋白诱导的免疫应答 将表征抗原并与应答进行比较 由抗原-弗氏佐剂乳剂或与 抗原-明矾佐剂混合物。 3.“润湿”现象的分子机制 将被研究。 将寻求克服这一问题的方法 控制释放的过程中经常遇到的问题 生物活性蛋白质 4.微囊化抗原的引发和诱导免疫应答的能力 将检测刺激T细胞应答。 此响应 将与完整病毒体诱导的结果进行比较。 成功的疫苗必须能够诱导免疫反应 这足以保护宿主免受不利的 病毒感染的后果。 这里描述的实验 旨在促进方法的发展， 这些技术可能会增加 病毒和亚病毒抗原作为成功的疫苗抗原。