EXPERIMENTAL LEPROSY VACCINE STUDIES

目标是：1)继续对正常猴子进行纵向观察 卡介苗或卡介苗+热灭活麻风杆菌免疫组 (HKML)，然后是现场ML挑战；2)确定： 对整个ML和ML抗原(Ag)进行体外原始细胞生成免疫； 血清抗(A)-PGL-I和A-LAM免疫球蛋白和IgM抗体的酶联免疫吸附试验 用来普鲁明测试反应性；和单核细胞亚群鉴定 在麻风皮损中用单抗染色检测表型标志和 用聚合酶链式反应方法鉴定细胞因子m-RNA；3) 确定免疫接种是否能预防临床症状的出现 麻风病；4)测定恒河猴(Rm)与煤烟芒果病的相对值 猴子(SMM)作为测试抗麻风疫苗的模型；以及5)评估 活体ML的临床、病理和免疫学纵向效应 在未接种卡介苗和卡介苗或卡介苗/卡介苗接种的RM和SMM中的挑战。 尽管近年来世界各地的麻风病例数量有所减少 多年来，我们对猴子的观察表明， 艾滋病通过增加艾滋病的易感性来扭转这一趋势- 感染麻风的接触者转变为麻风，并将现有病例转移到 L1末端的光谱，增加麻风杆菌在 环境。因此，艾滋病可能会增加传染和失控的风险 麻风病。 最好的麻风病预防药物是一种抗麻风疫苗，它将 对流行地区的高危人群进行保护性免疫。因此，我们将 评估卡介苗或卡介苗+HKML是否能提供这种保护 对麻风先生的指控。 我们还建议调查早期和顺序的性质 出现易感免疫因素可能与 对麻风的易感性或抵抗力，通过纵向观察， 利用新技术如麻风皮损内的免疫现象 作为细胞因子m-RNA在病变活检组织中的应用 以及以前被证明与倾向于 极型麻风的研究进展：原始细胞发生、抗体 对ML Ag和leproin皮肤测试的反应。在人类身上的研究已经 显示了长期存在的麻风病的最终结果，但这不符合伦理 在ML之前开始研究纵向未治疗的麻风是可行的 感染，了解最初的易感/耐药因素。这个 拟议的研究将试图通过搜索以下内容来解决这个问题 与敏感性/耐药性平行的免疫学参数的变化。

The goals are to: 1) continue longitudinal observations on normal monkeys and those immunized with BCG or BCG + heat-killed mycobacterium leprae (HKML) followed by challenge with live ML; 2) determine: the effects of immunization on in vitro blastogenesis to whole ML and to ML antigens (Ag); serum ELISA's for anti (A)-PGL-I and A-LAM IgG and IgM antibodies; skin test reactivity with lepromin; and mononuclear cell subset identifications in leprosy lesions by monoclonal Ab staining for phenotypic markers and cytokine profiles by a PCR method to identify cytokine m-RNA's; 3) determine if immunization protects against the appearance of clinical leprosy; 4) determine the relative value of rhesus (RM) vs sooty mangabey monkeys (SMM) as models for testing anti-leprosy vaccines; and 5) evaluate longitudinally the clinical, pathologic and immunologic effects of live ML challenge in unvaccinated and BCG- or BCG/HKML vaccinated RM and SMM. Although the number of leprosy cases worldwide has decreased in recent years, our observations in monkeys suggest that there is a potential for AIDS to reverse that trend by increasing the susceptibility of AIDS- infected leprosy contacts to leprosy and by shifting existing cases towards the LL end of the spectrum, increasing the presence of M. leprae in the environment. Thus AIDS may increase risk of contagion and loss of control of leprosy. The best leprosy preventative would be an anti-leprosy vaccine that would protectively immunize those at risk in endemic areas. Thus, we will evaluate whether or not BCG or BCG+ HKML can provide such protection against M. leprae. We also propose to investigate the nature of early and sequentually appearing predisposing immunologic factors that may be related to susceptibility or resistance to leprosy, by observing longitudinally, immunologic phenomena within leprosy lesions utilizing new technology such as cytokine m-RNA identifications in lesion biopsies using a PCR method, as well as techniques previously shown to be related to propensity to the development for the polar forms of leprosy: blastogenesis, antibody responses to ML Ag's and lepromin skin testing. Studies in humans have shown the end result of long-standing leprosy, but it is not ethically feasible to study longitudinally untreated leprosy beginning prior to ML infection, to learn the initial susceptibility/resistance factors. The proposed studies will attempt to address that issue by searching for changes in immunologic parameters that parallel susceptibility/resistance.