BINDING OF ALLERGENS TO LIPOSOMES FOR IMMUNOTHERAPY

过敏原与脂质体的结合用于免疫治疗

• 批准号: 3488790
• 负责人: ARISTO WOJDANI
• 金额: $ 5万
• 依托单位: IMMUNOSCIENCES LAB, INC.
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3488790
• 关键词: Ambrosia; allergens; antiallergic agents; chemical binding; dipeptides; dosage forms; enzyme linked immunosorbent assay; immunoglobulin E; immunological substance; immunomodulators; immunoregulation; immunotherapy; liposomes; plant extracts; radioimmunoassay

Within the last 25 years, researchers have attempted to develop extracts that would require less frequent immunization. The idea is to modify the chemical structure of the allergen in such a manner that reduces the allergenicity but promotes the immunogenicity. Recently, pliposomes and immune potentiators have been used to enhance the immune system in general and to promote the immunogenicity of many antigens in particular. Since for modification of allergens this approach has not yet been used by other investigators, in this study our major goal is to encapsulate standardized allergens and biological response modifiers (BRMs) to different liposomes and study the effect of this modification on their allergenicity and antigenicity using in vitro techniques. It is hoped that modification of allergen by binding to liposomes with or without BRMs will correct the faulty regulation in T cell function and may lead to production of IgG blocking antibodies but not IgE. To test this hypothesis, in Phase I it is planned to: 1. Encapsulate ragweed or June grass to different phospholipid composition (liposome) 2. Encapsulate ragweed or June grass and an immune potentiator such as acylated muramyl dipeptide (MDP) to liposomes. 3. Check the stability of the liposome encapsulated allergen and/or MDP by preparation of radiolabeled products and measuring radioactivity in the supermutants. These modified allergens will be examined in an in vitro model system developed for this purpose. Mononuclear cells from control and atopic patients will be incubated in tissue culture system with different concentrations of soluble ragweed, June grass or liposome encapsulated allergen with or without MDP, for up to 12 days. At different intervals (Day 1, 7, 12), samples from the supernatant will be measured for the level of histamine released from the basophils and for the amount of allergen specific IgG or IgE, by RIA or EIA respectively. In addition, mononuclear cells will be counted for the numbers of lymphocytes, basophils and for antigen-specific IgE-plaque forming cells. Decrease in the numbers of IgE plaque forming cells and IgE content with an increase in allergen specific blocking IgG antibodies in the culture system containing liposome encapsulated allergens, will be indicative of reduced allergenicity but enhanced antigenicity. During Phase II additional allergens by both encapsulation as well as cross linking to liposomes will be tested.

在过去 25 年里，研究人员尝试开发提取物 这将需要较少的免疫频率。 想法是修改 过敏原的化学结构，以减少 致敏性，但促进免疫原性。 最近，脂质体和 免疫增强剂已被用来增强整体免疫系统 尤其是促进许多抗原的免疫原性。 自从 对于过敏原的修饰，这种方法尚未被其他公司使用 研究人员，在这项研究中，我们的主要目标是封装标准化 针对不同脂质体的过敏原和生物反应调节剂 (BRM) 并研究这种修饰对其致敏性的影响 使用体外技术的抗原性。 希望修改 通过与带有或不带有 BRM 的脂质体结合来消除过敏原将纠正 faulty regulation in T cell function and may lead to production of IgG 阻断抗体但不阻断 IgE。 为了检验这个假设，在第一阶段 计划： 1. 将豚草或六月草封装成不同的磷脂组合物 （脂质体） 2. 封装豚草或六月草和免疫增强剂，例如 酰化胞壁酰二肽（MDP）至脂质体。 3. 检查脂质体封装的过敏原和/或 MDP 的稳定性 放射性标记产品的制备和放射性测量 超级突变体。 这些改良的过敏原将在体外模型系统中进行检查 为此目的而开发的。 对照和特应性单核细胞 患者将在组织培养系统中培养不同的 可溶性豚草、六月草或封装的脂质体的浓度 含或不含 MDP 的过敏原，最长 12 天。 不同时间间隔 （第 1、7、12 天），将测量上清液样品的水平 嗜碱性粒细胞释放的组胺和过敏原的量 特异性 IgG 或 IgE，分别通过 RIA 或 EIA 检测。 此外，单核 将计算淋巴细胞、嗜碱性粒细胞的数量以及 抗原特异性 IgE 斑块形成​​细胞。 IgE 数量减少 斑块形成细胞和 IgE 含量随着过敏原特异性的增加 含有脂质体的培养系统中阻断 IgG 抗体 封装的过敏原，将表明过敏性降低，但 抗原性增强。 在第二阶段期间，双方都产生了额外的过敏原 将测试封装以及与脂质体的交联。