EXPERIMENTAL LEPROSY & VACCINE STUDIES IN MONKEYS: MYCOBACTERIA

我们分析和评估了收集到的纵向免疫学数据， 接种（PV）后3-4年（使用活BCG或BCG +） 热灭活麻风分枝杆菌，HKML），加强后（PB）和 用活ML进行攻毒后（PC）。 恒河猴（RM）[少杆菌 （PB）-倾向，作为一个物种]在临床上受到显著保护， BCG或BCG + HKML;无菌白眉猴（SMM）[多杆菌 （MB）-倾向，作为一个物种]部分受到BCG单独的保护，但 临床上对BCG + HKML更敏感。 一致 在临床结果和胚细胞生成反应之间观察到相似之处 血单个核细胞对ML抗原和结核菌素、血清 抗酚糖脂-I（PGL-I）抗体同种型（IgG和IgM） 应答，血清PGL-I抗原水平，血淋巴细胞亚群 携带CD 4、CD 8、CD 16、CD 20、CD 4 CD 29和CD 4 CD 45表型标记 和麻风菌素皮试结果 有多种复杂的， 免疫应答中相互关联的剂量依赖关系 决定麻风易感性/耐药性的ML抗原。 的 机制可能涉及RM和SMM之间的细微差异， 细胞因子的产生和/或应答，其模拟了 具有PB与MB倾向的个体人类。 研究正在 通过PCR确定比较细胞因子谱的进展 在本研究中，从动物体内获得的病变活检， 帮助

We analyzed and evaluated longitudinal immunologic data gathered over a 3-4 year period post vaccination (PV) (with live BCG or BCG + heat-killed Mycobacterium leprae, HKML), post-boosting (PB) and post-challenge (PC) with live ML. Rhesus monkeys (RM) [paucibacillary (PB)-prone, as a species] were significantly protected clinically by BCG or BCG + HKML; sooty mangabey monkeys (SMM) [multibacillary (MB)-prone, as a species] were partially protected by BCG alone, but were rendered clinically more susceptible by BCG + HKML. Consistent parallels were seen between clinical results and blastogenic responses of blood mononuclear cells to ML antigens and to tuberculin, serum anti-phenolic glycolipid-I (PGL-I) antibody isotype (IgG & IgM) responses, serum PGL-I antigen levels, blood lymphocyte subsets carrying CD4, CD8, CD16, CD20, CD4CD29 and CD4CD45 phenotypic markers and lepromin skin test results. There are multiple complex, interrelated dose-dependent relationships in immunologic responses to ML antigens that determine leprosy susceptibility/resistance. The mechanisms may involve subtle differences between RM and SMM in cytokine production and/or responses, which model responses in individual humans with PB vs MB predispositions. Studies are in progress to determine comparative cytokine profiles by PCR in longitudinally-obtained lesion biopsies from animals in this study to help