EXPERIMENTAL LEPROSY/VACCINE STUDIES IN MANGABEYS

白眉猴的麻风病/疫苗实验研究

• 批准号: 3565460
• 负责人: BOBBY J GORMUS
• 金额: $ 49.55万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3565460
• 关键词: Cercopithecidae; Edentata; Mycobacterium leprae; antibody dependent killer cell; antibody formation; bacterial antigens; bacterial vaccines; cell population study; chemical binding; chickens; cow; disease /disorder model; goats; immune tolerance /unresponsiveness; immunization; immunoglobulin A; immunoglobulin G; immunoglobulin M; interferons; interleukin 1; interleukin 2; laboratory mouse; laboratory rabbit; leprosy; leukocyte activation /transformation; lymphocyte; mitogens; model design /development; monoclonal antibody; monocyte; protein biosynthesis; sheep; tissue /cell culture; western blottings

The goals of this proposal are: 1) to evaluate protective immunity in sooty mangabey monkeys (Cercocebus atys) by challenge with viable Mycobacterium leprae after immunization with live BCG alone or in combination with two doses of heat killed, whole M. leprae. 2) to evaluate the clinical, pathologic and immunologic effects of M. leprae infection in mangabeys after vaccination and throughout the course of disease and treatment and 3) to study the nature of the immune defects in mangabey with LL leprosy. There are 12 to 15 million leprosy patients worldwide, many of them in underdeveloped areas where chemotherapy is impractical and/or too expensive. The development of an effective vaccine would obviate the necessity for therapy. Monkeys are phylogenetically similar to man, and lepromatous (L) leprosy in the mangabey monkey is clinically and immunologically similar to humans. Immunity will be assessed longitudinally before and after vaccination of mangabey monkeys by: skin testing with soluble Rees M. leprae to determine the effectiveness of vaccination. We will study immune parameters longitudinally in control, vaccinated and experimentally infected mangabeys to monitor the dynamics of leprosy-induced changes relative to the observed cyclic rhythm. We will compare control mangabeys to those with early and late LL leprosy (both disseminated and nondisseminated) to dissect the mechanism of the immune unresponsiveness induced in managabey by LL leprosy. In these studies we will monitor the following in blood mononuclear cells (MNC). 1) in vitro responses to mitogens (Con A, PHA and PWM) and to Dharmendra lepromin (D-lep); 2) binding by monoclonal antibodies; and 3) pokeweed mitogen-induced immunoglobulin plaque-forming cell numbers. Levels of serum antibodies (IgG, IgM, IgA) to M. leprae-specific phenolic glycolipid 1 antigen will be determined. Lymphocytes (L) and monocytes (MO) will be separated into subpopulations and will studied separately and in various recombinations for normal responses to D-lep. Levels of lymphokine production [gamma-interferon (gamma-IFN); interleukin 1 (IL-1) and IL-2] by the various MNC subpopulations will be determine. Pure lymphokines will be added back to cell fractions from mangabeys with LL in attempts to reconstitute normal responses to mitogens and to D-lep.

该提议的目标是：1）评估保护性免疫 通过可行的挑战 单独或现场BCG免疫后麻风分枝杆菌 结合两剂杀死的热量，整个M. Leprae。 2）到 评估Leprae的临床，病理和免疫学作用 疫苗接种后和整个过程中的芒果感染 疾病和治疗以及3）研究免疫缺陷的性质 Mangabey与LL麻风病。 全球有12至1500万麻风病患者，其中许多在 化学疗法不切实际和/或也是/或 昂贵的。有效疫苗的开发将消除 需要治疗的必要性。猴子在系统发育上与人相似，并且 Mangabey猴子中的麻风病（L）麻风病是临床上的 免疫学上与人类相似。免疫将被评估 曼加比猴子接种前后，纵向蒙受纵向：皮肤 使用可溶性Rees M. Leprae测试以确定的有效性 疫苗接种。我们将在控制中纵向研究免疫参数， 接种疫苗和实验感染的芒果以监测动力学 相对于观察到的环状节奏，麻风病诱导的变化的变化。我们 将将控制芒果与患有早期和晚期麻风病的人进行比较 （均传播和非染色），以剖析 LL Leprosy在Managabey引起的免疫无反应性。在这些 研究我们将在血液单核细胞（MNC）中监测以下内容。 1）在体外对有丝分裂剂（Con A，PHA和PWM）和Dharmendra的反应 Lepromin（D-Lep）; 2）通过单克隆抗体结合； 3）pokeweed 有丝分裂原诱导的免疫球蛋白斑块形成细胞数。水平 血清抗体（IgG，IgM，Iga） 将确定糖脂1抗原。 淋巴细胞（L）和单核细胞（MO）将分为亚群 并将分别研究并在各种重组中以正常研究 对D-Lep的响应。淋巴因子产生水平[伽马互换 （γ-IFN）;白介素1（IL-1）和IL-2]由各种MNC 将确定亚群。纯淋巴因子会添加回到 LL的Mangabeys的细胞分数试图重建正常 对有丝分裂剂和D-LEP的反应。