ENHANCING MUCOSAL IMMUNE RESPONSES BY MICROENCAPSULATION

通过微囊化增强粘膜免疫反应

• 批准号: 6626466
• 负责人: Paul A. Offit
• 金额: $ 43.75万
• 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 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626466
• 关键词: B lymphocyte; Rotavirus; T lymphocyte; antibody formation; antigen presenting cell; gastrointestinal epithelium; immunologic memory; laboratory mouse; leukocyte activation /transformation; microcapsule; microorganism immunology; mucosal immunity; oral administration; rotavirus vaccines; tissue /cell culture; vaccine development; virus antigen

DESCRIPTION (Adapted from applicant's abstract): Whereas protection following natural infection with systemic viruses (such as measles, mumps, rubella, or varicella) is usually life-long and complete (1), protection following infection with mucosal viruses (such as rotavirus, influenza virus or respiratory syncytial virus) is usually short-lived and incomplete (2). Two observations might explain these differences. First, antibody-secreting cells (ASC) at mucosal surfaces after natural infection or immunization (primary ASC) are short-lived (3). Second, the time required for generation of secondary ASC derived from memory B cells is often longer than the incubation periods of most mucosal pathogens. Therefore, development of vaccines that provide long-lived and complete protection against mucosal pathogens will depend upon either prolonging primary ASC after immunization or hastening the onset of secondary ASC after challenge. To enhance virus-specific mucosal immune responses, we recently developed a system of microencapsulation based on the ionic linkage of aqueous polymers and aqueous amines (10). We found that microcapsules enhance the magnitude of primary and secondary rotavirus-specific ASC and enhance protection against rotavirus challenge. Although the mechanism by which microcapsules enhance protective virus-specific immune responses remains unclear, we found that microcapsules containing rotavirus might select for antigen-presenting cells (APC) different from and perhaps more efficient that those involved during natural infection. Using microencapsulated and unencapsulated preparations of rotavirus, we will determine whether APC type (i.e. dendritic cells, macrophages, B cells, or intestinal epithelial cells) alters primary or secondary ASC responses. In addition, by biologically or chemically modifying microcapsules, we will determine whether alteration in the type of APC recruited during mucosal infection, or alteration in the kinetics of antigen presentation, modifies protective immune responses. The availability of microencapsulated virus provides a unique opportunity to understand the relationship between APC and protective mucosal immune responses.

描述（改编自申请人的摘要）：鉴于保护如下 系统性病毒的自然感染（如麻疹、腮腺炎、风疹或 水痘）通常是终生且完整的 (1)，保护如下 粘膜病毒感染（如轮状病毒、流感病毒或 呼吸道合胞病毒）通常是短暂且不完整的 (2)。二 观察可能可以解释这些差异。一、抗体分泌细胞 (ASC) 自然感染或免疫后粘膜表面（原发 ASC） 是短暂的（3）。二、生成二次ASC所需时间 来自记忆 B 细胞的潜伏期通常比大多数 B 细胞的潜伏期长。 粘膜病原体。因此，开发能够提供长期存活的疫苗 对粘膜病原体的完全保护将取决于 免疫后延长原发性 ASC 或加速继发性 ASC 的发生 挑战后ASC。为了增强病毒特异性粘膜免疫反应，我们 最近开发了一种基于离子键的微胶囊系统 水性聚合物和水性胺(10)。我们发现微胶囊增强了 原发性和继发性轮状病毒特异性 ASC 的程度并增强 防止轮状病毒的挑战。尽管其机制 微胶囊增强保护性病毒特异性免疫反应 不清楚，我们发现含有轮状病毒的微胶囊可能会选择 抗原呈递细胞（APC）不同于并且可能更有效 那些参与自然感染的人。使用微胶囊和 轮状病毒的未封装制剂，我们将确定是否为APC类型 （即树突状细胞、巨噬细胞、B 细胞或肠上皮细胞） 改变初级或次级 ASC 反应。此外，通过生物学或 对微胶囊进行化学修饰，我们将确定是否改变 粘膜感染期间募集的 APC 类型或动力学改变 抗原呈递，改变保护性免疫反应。可用性 微囊病毒的研究提供了一个独特的机会来了解 APC 与保护性粘膜免疫反应之间的关系。