EXPERIMENTAL LEPROSY VACCINE STUDIES

目标是：1）继续对正常猴子进行纵向观察 BCG或BCG +热灭活麻风分枝杆菌免疫组 （HKML），然后用活ML激发; 2）确定： 对整个ML和ML抗原（Ag）进行体外胚细胞生成免疫; 抗（A）-PGL-I和A-LAM IgG和IgM抗体的血清ELISA;皮肤 用麻风菌素测试反应性;和单核细胞亚群鉴定 用单克隆抗体染色法检测麻风病皮损中的表型标志物， 通过PCR方法鉴定细胞因子m-RNA的细胞因子谱; 3） 确定免疫接种是否可以防止临床表现 4）测定恒河猴（RM）与白眉猴（M. mangabey）的相对值 猴（SMM）作为测试抗麻风疫苗的模型;和5）评估 纵向研究肝ML的临床、病理和免疫学效应 在未接种疫苗和接种BCG或BCG/HKML的RM和SMM中进行攻毒。 虽然近年来全球麻风病例数量有所减少， 多年来，我们在猴子身上的观察表明， 通过增加艾滋病的易感性来扭转这一趋势- 感染麻风病的接触者，并将现有病例转向 光谱的LL端，增加M的存在。麻风病在 环境 因此，艾滋病可能会增加传染和失控的风险 麻风病 最好的麻风病预防措施是抗麻风病疫苗， 对流行地区的高危人群进行保护性免疫接种。 因此，我们将 评估BCG或BCG+ HKML能否提供此类保障 分支杆菌麻风病人 我们还建议调查的性质，早期和顺序 出现易患免疫因素，可能与 对麻风病的易感性或抗性，通过纵向观察， 利用新技术， 作为使用PCR方法在病变活检中鉴定细胞因子m-RNA，作为 以及先前显示的与 麻风极性型的发展：胚细胞发生，抗体 对ML Ag和麻风菌素皮肤试验的反应。 人体研究 显示了长期存在的麻风病的最终结果，但这不是道德上的， 可行的纵向研究未治疗的麻风开始之前ML 感染，以了解最初的易感性/耐药因素。 的 拟议的研究将试图通过寻找 与易感性/耐药性平行的免疫学参数变化。

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.