Steinberger A, Slutzky G M, El-On J, Greenblatt C L
Exp Parasitol. 1984 Dec;58(3):223-9. doi: 10.1016/0014-4894(84)90038-9.
Excreted factor, an immunosuppressive, acidic polysaccharide released by promastigotes of Leishmania tropica major in culture, was chemically crosslinked to the synthetic adjuvant muramyl dipeptide via the bifunctional imidoester dimethyladipimidate and poly-L-lysine. This conjugate, an uncrosslinked mixture of the components, or each of the components alone were injected one to three times into different groups of 8- to 12-week-old C3H mice. The mice were challenged 2 weeks after the last injection with 2 X 10(6) promastigotes of L. t. major in the base of the tail. For the next 5 weeks, the animals were monitored for number of parasites and size of the lesion which developed at the site of the challenge. Mice receiving one intraperitoneal injection of the conjugate were partially protected against challenge. Treated animals had higher initial parasite numbers but showed a more rapid clearing of the parasites. Furthermore, the treated animals developed smaller lesions that healed quicker than did those of the control groups. Multiple injections, or injection into a footpad, rather than intraperitoneally, reduced the ability to elicit a protective response. On the other hand, muramyl dipeptide injected into a footpad was partially protective. Antibody production to excreted factor, which was measured by indirect hemagglutination of sensitized erythrocytes, was detected after challenge in mice which had received conjugate or conjugate components. A delayed hypersensitivity reaction (measured by skin testing) was not detected in any of the groups prior to challenge.
排泄因子是热带利什曼原虫前鞭毛体在培养过程中释放的一种免疫抑制性酸性多糖，通过双功能亚胺酯二甲基己二酰亚胺和聚-L-赖氨酸与合成佐剂胞壁酰二肽进行化学交联。将这种缀合物、各成分的未交联混合物或单独的各成分分别注射1至3次到不同组的8至12周龄C3H小鼠体内。在最后一次注射后2周，用2×10⁶个热带利什曼原虫前鞭毛体在小鼠尾巴根部进行攻击。在接下来的5周内，监测动物体内寄生虫数量以及攻击部位出现的病变大小。接受一次腹腔注射缀合物的小鼠对攻击有部分保护作用。经处理的动物初始寄生虫数量较多，但寄生虫清除速度更快。此外，经处理的动物出现的病变较小，愈合速度比对照组更快。多次注射或注射到脚垫而非腹腔内会降低引发保护反应的能力。另一方面，注射到脚垫的胞壁酰二肽有部分保护作用。在接受缀合物或缀合物成分的小鼠受到攻击后，通过致敏红细胞间接血凝法检测到对排泄因子的抗体产生。在攻击前，任何一组均未检测到迟发型超敏反应（通过皮肤试验测量）。
