Gicheru M M, Olobo J O, Anjili C O
Leishmaniasis Programme, Institute of Primate Research, National Museums of Kenya, Karen, Nairobi.
Exp Parasitol. 1997 Feb;85(2):109-16. doi: 10.1006/expr.1996.4117.
The study was aimed at analyzing immunological cross-reactivity between Leishmania major and Leishmania donovani and possible cross-protection between the two parasite species in the vervet monkey model of the disease. Nine vervet monkeys (Cercopithecus aethiops) from the institute animal colony were sued in the study. Five of the animals had been previously infected with L. donovani but had remained asymptomatic while the other four animals were naive and comprised the control group. Immunological responses to both L. major and L. donovani antigens in the five animals with prior exposure to L. donovani were examined before challenge. High antibody titers to the two antigens were demonstrated in an enzyme-linked immunosorbent assay, but the antibody titers to L. donovani were significantly higher than those to L. major (P < 0.005). Positive in vitro peripheral blood leucocyte (PBL) proliferation to L. major and L. donovani antigens was also demonstrated, but there was no significant difference in the response to the two antigens (P > 0.1). High and varying levels of interferon gamma (IFN-gamma) were secreted in PBL from the five vervet monkeys when stimulated with L. major antigen, but vervet monkey 1296 secreted marginal levels of IFN-gamma. When the animals were challenged intradermally with 1 x 10(5) virulent L. major promastigotes mixed with sandfly vector salivary gland lysate all four vervet monkeys in the control group developed nodules of varying sizes at the inoculation sites that eventually ulcerated. However, nodule formation and ulceration occurred at different times among these animals. The other five animals (animals with prior exposure to L. donovani) did not pick up the infection at all, but one animal from this group, vervet monkey 1296, developed a transient lesion that healed within 9 weeks, the same animal that had been shown to secrete low levels of IFN-gamma. The results demonstrate high cross-reactivity between L. donovani and L. major and that L. donovani protects against L. major infections. This finding is important for vaccine development studies against leishmaniasis.
该研究旨在分析硕大利什曼原虫和杜氏利什曼原虫之间的免疫交叉反应，以及在该疾病的黑长尾猴模型中这两种寄生虫物种之间可能存在的交叉保护作用。研究使用了来自该研究所动物饲养群体的9只黑长尾猴（非洲绿猴）。其中5只动物先前感染过杜氏利什曼原虫，但一直无症状，而另外4只动物未感染过，作为对照组。在进行攻击之前，检测了5只先前接触过杜氏利什曼原虫的动物对硕大利什曼原虫和杜氏利什曼原虫抗原的免疫反应。在酶联免疫吸附试验中显示出对这两种抗原的高抗体滴度，但对杜氏利什曼原虫的抗体滴度显著高于对硕大利什曼原虫的抗体滴度（P < 0.005）。还证明了体外外周血白细胞（PBL）对硕大利什曼原虫和杜氏利什曼原虫抗原的阳性增殖，但对这两种抗原的反应没有显著差异（P > 0.1）。当用硕大利什曼原虫抗原刺激时，5只黑长尾猴的PBL分泌出高水平且变化的γ干扰素（IFN-γ），但黑长尾猴1296分泌的IFN-γ水平较低。当用1×10⁵个有毒力的硕大利什曼原虫前鞭毛体与白蛉载体唾液腺裂解物混合进行皮内攻击时，对照组的所有4只黑长尾猴在接种部位出现了大小不同的结节，最终形成溃疡。然而，这些动物中结节形成和溃疡出现的时间不同。另外5只动物（先前接触过杜氏利什曼原虫的动物）根本没有感染，但该组中的一只动物，黑长尾猴1296，出现了一个短暂病变，在9周内愈合，这只动物就是之前显示分泌低水平IFN-γ的那只。结果表明杜氏利什曼原虫和硕大利什曼原虫之间存在高度交叉反应，并且杜氏利什曼原虫可预防硕大利什曼原虫感染。这一发现对于利什曼病疫苗开发研究具有重要意义。
