Scott P, Pearce E, Natovitz P, Sher A
J Immunol. 1987 Jul 1;139(1):221-7.
BALB/c mice can be protected against a fatal Leishmania major infection by immunization with whole radio-attenuated promastigotes; however, neither the antigens responsible for protection nor the protective immunologic mechanisms have been defined. In this study, the ability of promastigote fractions to elicit similar immunity to that obtained with whole organisms, and the immune responses associated with such protection were analyzed. Intraperitoneal immunization with a soluble, membrane-free parasite extract was found to induce protection against L. major challenge equal to that obtained with whole organisms. Induction of immunity (89% protection in seven experiments) was most effective with 100 micrograms of the soluble leishmanial antigen (SLA) and required concomitant injection of the bacterial adjuvant, Corynebacterium parvum (CP), followed by an i.p. boost of SLA alone 1 wk later. Vaccinated animals exhibited Leishmania-specific cell-mediated immunity, as assessed both by lymphocyte transformation and the production of macrophage-activating factors (MAF). In addition, although SLA + CP-immunized mice failed to exhibit delayed-type hypersensitivity (DTH) before challenge, splenic lymphocytes from these mice could transfer a local DTH reaction to naive recipients. Immunization also induced the production of antibodies against two major metabolically labeled proteins of m.w. 30,000 and 53,000, but failed to stimulate a detectable humoral response against promastigote surface antigens. Thus, these experiments demonstrate that vaccine-induced immunity against cutaneous leishmaniasis is strongly associated with the induction of cell-mediated immunity, but does not require the development of an antibody response to promastigote surface antigens. In addition, these studies establish the feasibility of employing soluble, nonmembrane-derived parasite material as a source of protective immunogens.
通过用经辐射减毒的完整前鞭毛体免疫，可使BALB/c小鼠免受致命的硕大利什曼原虫感染；然而，负责提供保护的抗原以及保护性免疫机制均未明确。在本研究中，分析了前鞭毛体组分引发与完整生物体所获免疫相似的免疫能力，以及与这种保护相关的免疫反应。发现用可溶性、无膜的寄生虫提取物进行腹腔免疫可诱导出与完整生物体所获保护相当的针对硕大利什曼原虫攻击的保护作用。用100微克可溶性利什曼原虫抗原（SLA）诱导免疫（在七项实验中有89%的保护率）最为有效，且需要同时注射细菌佐剂微小棒状杆菌（CP），随后在1周后单独腹腔注射SLA进行加强免疫。通过淋巴细胞转化和巨噬细胞激活因子（MAF）的产生评估，接种疫苗的动物表现出利什曼原虫特异性细胞介导免疫。此外，尽管经SLA + CP免疫的小鼠在攻击前未表现出迟发型超敏反应（DTH），但这些小鼠的脾淋巴细胞可将局部DTH反应传递给未免疫的受体。免疫还诱导产生了针对两种主要代谢标记蛋白（分子量分别为30,000和53,000）的抗体，但未能刺激出针对前鞭毛体表面抗原的可检测体液反应。因此，这些实验表明，疫苗诱导的针对皮肤利什曼病的免疫与细胞介导免疫的诱导密切相关，但不需要对前鞭毛体表面抗原产生抗体反应。此外，这些研究确立了使用可溶性、非膜来源的寄生虫材料作为保护性免疫原来源的可行性。
