IMMUNE ENHANCEMENT OF POLIOVIRUS ANTIGENICITY

拟议研究的目的是测试以下项目的可行性 通过增强病毒抗原的免疫应答 微胶囊在缓释生物聚合物中的应用。因为 脊髓灰质炎病毒抗原的免疫原性已被广泛研究 特征是，脊髓灰质炎病毒亚单位抗原提供了一种极好的 用于测试控释能力的模型系统 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 使用生物相容聚合物的反应和可行性 病毒抗原的控制释放和呈递 免疫，并有可能增加诱导 中和抗体。 要实现这些目标： 1.单个脊髓灰质炎病毒抗原将被封装到 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- 嵌入的聚合物将进行物理表征，并 在体外和小鼠体内测定的释放曲线。 2.免疫小鼠产生的抗体反应 将对微囊化脊髓灰质炎病毒抗原进行表征。 微囊化牛血清白蛋白诱导免疫应答 将对抗原进行表征，并与反应进行比较 由无抗原佐剂乳剂或与 抗原-明矾佐剂混合物。 3.“润湿”现象的分子机制 将会被研究。将寻求克服这一问题的方法 在控制释放方面经常遇到问题 具有生物活性的蛋白质。 4.微囊化抗原诱导和 刺激T细胞反应将被检测。这一反应 将与完整的病毒粒子诱导的病毒相比较。 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 旨在帮助开发方法和 技术，这些技术可能会增加 病毒和亚病毒抗原成为成功的疫苗抗原。

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.