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?

已发现病毒或细菌抗原的微胶囊化 增强实验动物的抗原特异性免疫反应。这 这些发现的前景鼓励了微胶囊的研究 成年志愿者体内的抗原。然而，人们对此知之甚少 微胶囊增强免疫反应的机制 微胶囊诱导免疫反应的能力 防止挑战，或微胶囊化的潜力 扰乱抗原特异性免疫反应。 例如，微 口服接种的封装病毒可能会绕过抗原呈递 由粘膜上皮细胞选择巨噬细胞摄取抗原， 并保护病毒免于接触粘膜蛋白酶。 这些变化可能 扰乱病毒特异性体液免疫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)。 我们最近开发了一种使用水性微胶囊的系统 阴离子聚合物和水胺（带电薄膜微胶囊）。这 水溶性试剂封装传染性病毒的能力 消除了对与有机物相关的抗原性丧失的担忧 基于溶剂的微胶囊系统。利用肠道 病原体，轮状病毒，我们发现带电薄膜微胶囊具有 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问题来扩展这些观察结果 问题：1）微胶囊化的机制是什么？ 病毒增强病毒特异性免疫力？ 2）小鼠是否口服接种 含有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之间的平衡 细胞反应？ 3) 轮状病毒的微囊化是否会改变 病毒特异性中和抗体的良好抗原特异性 或CTL？ 4）微囊病毒口服接种小鼠吗 或病毒蛋白增强免疫能力以防止感染 挑战？