EXPERIMENTAL LEPROSY/VACCINE STUDIES IN MANGABEYS

这项建议的目标是：1)评估 煤烟黑尾猴(Cercocebus Atys)被活体挑战 活卡介苗单独或联合免疫后的麻风分枝杆菌 再加上两个剂量的热致死，整个麻风杆菌。2)至 评估麻风杆菌的临床、病理和免疫学效应 接种疫苗后和整个疫苗接种过程中芒果鼠的感染 疾病和治疗；3)研究免疫缺陷的性质 曼加比患有LL麻风病。 全世界有1200万至1500万麻风病患者，其中许多人在 不发达地区，化疗不切实际和/或 很贵的。开发一种有效的疫苗将消除 治疗的必要性。猴子在系统发育上与人类相似，而且 黑尾猴(L)麻风病的临床和病理特点 在免疫学上与人类相似。豁免权将被评估 恒河猴纵向接种前后：皮肤 用可溶性麻风杆菌进行测试，以确定其有效性 接种疫苗。我们将在对照中纵向研究免疫参数， 接种疫苗并实验感染芒果蜂以监测其动态 麻风引起的变化相对于观察到的周期节律。我们 会将对照黑猩猩与早期和晚期LL麻风病患者进行比较 (包括播散性和非播散性)来剖析 LL麻风引起的管理中的免疫无反应。在这些 研究中，我们将监测血液单个核细胞(MNC)中的以下内容。 1)体外对有丝分裂原(ConA、PHA和PWM)和丹参的反应 Leproin(D-lep)；2)单抗结合；3)商陆 丝裂原诱导的免疫球蛋白空斑形成细胞数。级别 血清抗麻风杆菌特异性酚类抗体(Ig G、Ig M、Ig A) 糖脂1抗原将被测定。 淋巴细胞(L)和单核细胞(MO)将分为亚群 并将分别研究和在各种重组中正常 对D-LEP的反应。淋巴因子产生水平(γ-干扰素 (γ-干扰素；白介素1(IL-1)和白介素2) 将确定亚群。纯淋巴因子将被重新添加到 试图恢复正常的患有LL的芒果鸟细胞组分 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.