EXPERIMENTAL LEPROSY/VACCINE STUDIES IN MANGABEYS

该提案的目标是：1）评估保护性免疫力， 用活猴挑战乌黑白眉猴（Cercocebus atys） 单独或联合接种活卡介苗后的麻风分枝杆菌 结合两种剂量的热杀死，整个M。麻风病人2)到 评价M.麻风 在接种疫苗后和整个过程中， 疾病和治疗和3）研究免疫缺陷的性质， 患有麻风病的白眉猴 全世界有1200万至1500万麻风病人，其中许多人在 化疗不切实际和/或过于 贵了研制出有效的疫苗， 治疗的必要性。猴子在遗传学上与人类相似， 白眉猴的瘤型麻风病在临床上和 在免疫学上与人类相似。将评估免疫力 白眉猴接种前后的纵向：皮肤 用可溶性Rees M.麻风病，以确定有效性 预防针我们将在对照组中纵向研究免疫参数， 接种疫苗和实验感染的白眉猴， 麻风病引起的变化相对于观察到的周期性节律。我们 将对照白眉猴与早期和晚期LL麻风病的白眉猴进行比较 (both传播和非传播），以剖析的机制， LL型麻风致免疫无反应性在这些 研究中，我们将在血液单核细胞（MNC）中监测以下内容。 1)体外对有丝分裂原（Con A，PHA和PWM）和对达摩陀罗的反应 麻风菌素（D-lep）; 2）单克隆抗体结合; 3）美洲商陆 丝裂原诱导的免疫球蛋白空斑形成细胞数。水平 血清抗M.麻风特异性酚 将测定糖脂1抗原。 将淋巴细胞（L）和单核细胞（MO）分离为亚群 并将单独研究，并在各种重组正常 对D-Lep的回应淋巴因子产生水平[γ-干扰素 （γ-干扰素）;白细胞介素1（IL-1）和IL-2]的各种MNC 将确定亚群。纯淋巴因子将被添加回 来自患有LL的白眉猴的细胞组分试图重建正常的 对有丝分裂原和D-lep的反应。

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.