ENHANCEMENT OF IMMUNOGENICITY BY MICROENCAPSULATION

通过微胶囊化增强免疫原性

• 批准号: 2429379
• 负责人: Paul A. Offit
• 金额: $ 26.46万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2429379
• 关键词: Rotavirus; antibody specificity; antigen presenting cell; blocking antibody; cytokine; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; gut associated lymphoid tissue; immunofluorescence technique; laboratory mouse; microcapsule; microorganism immunology; neutralizing antibody; nonhuman therapy evaluation; oral administration; recombinant virus; rotavirus vaccines; tissue /cell culture; vaccinia virus; virus antigen; virus protein; virus replication

Microencapsulation of viral or bacterial antigens has been found to enhance antigen-specific immune responses in experimental animals. The promise of these findings has encouraged studies of microencapsulated antigens in adult volunteers. However, little is known about the mechanisms by which microencapsulation enhances the immune response, the capacity of microencapsulation to induce an immune response which protects against challenge, or the potential for microencapsulation to perturb antigen-specific immune responses. For example, micro- encapsulated viruses inoculated orally may bypass antigen presentation by mucosal epithelial cells, select for antigen uptake by macrophages, and protect virus from exposure to mucosal proteases. These changes may perturb the balance between virus-specific humoral and cellular immune responseS or alter the proteins recognized by virus-specific antibodies or cytotoxic T lymphocytes (CTLs). We recently developed a system of microencapsulation using aqueous anionic polymers and aqueous amines (charged-film microcapsules). The capacity of water-soluble reagents to encapsulate infectious virus obviates concerns about loss of antigenicity associated with organic solvent-based systems of microencapsulation. Using the intestinal pathogen, rotavirus, we found that charged-film microcapsules have the capacity to enhance rotavirus immunogenicity after oral inoculation of mice. We will extend these observations by addressing the following questions: 1) What are the mechanisms by which microencapsulation of virus enhances virus-specific immunity? 2) Does oral inoculation of mice with microencapsulated preparations of rotavirus or rotavirus proteins alter the magnitude of or balance between virus-specific humoral and cellular responses? 3) Does microencapsulation of rotavirus alter the fine antigenic specificities of virus-specific neutralizing antibodies or CTLs? 4) Does oral inoculation of mice with microencapsulated virus or viral proteins enhance the capacity of immunization to protect against challenge?

已经发现病毒或细菌抗原的微囊泡是 增强实验动物中抗原特异性免疫反应。这 这些发现的承诺鼓励了对微囊化的研究 成人志愿者的抗原。但是，关于 微囊化增强免疫反应的机制， 微囊化的能力诱导免疫反应，该免疫反应 防止挑战，或微塑料的潜力 敏捷抗原特异性免疫反应。 例如，微型 接种口服的封装病毒可能绕过抗原表现 通过粘膜上皮细胞，选择巨噬细胞的抗原吸收， 并保护病毒免于暴露于粘膜蛋白酶。 这些变化可能 扰动病毒特异性体液和细胞免疫之间的平衡 反应或改变病毒特异性抗体识别的蛋白质 或细胞毒性T淋巴细胞（CTL）。 我们最近使用水性开发了一个微囊泡系统 阴离子聚合物和水胺（带电膜微胶囊）。这 水溶性试剂封装感染性病毒的能力 消除对有机抗原性丧失的担忧 基于溶剂的微囊化系统。使用肠道 病原体，轮状病毒，我们发现带电的电影微胶囊具有 口服接种后增强轮状病毒免疫原性的能力 老鼠。我们将通过解决以下内容来扩展这些观察结果 问题：1）微囊化的机制是什么 病毒增强了病毒特异性免疫力？ 2）对小鼠进行口服接种 轮状病毒或轮状病毒蛋白的微囊制剂 改变病毒特异性体液和平衡的大小或平衡 细胞反应？ 3）轮状病毒的微囊化改变了 病毒特异性中和抗体的精细抗原特异性 还是CTL？ 4）用微囊病毒对小鼠进行口服接种 或病毒蛋白增强免疫能力防止 挑战？