Departamento de Farmacologia, Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil.
Microbes Infect. 2010 Nov;12(12-13):967-77. doi: 10.1016/j.micinf.2010.06.008. Epub 2010 Jul 1.
Leishmania chagasi and Leishmania amazonensis are the etiologic agents of different clinical forms of human leishmaniasis in South America. In an attempt to select candidate antigens for a vaccine protecting against different Leishmania species, the efficacy of vaccination using Leishmania ribosomal proteins and saponin as adjuvant was examined in BALB/c mice against challenge infection with both parasite species. Mice vaccinated with parasite ribosomal proteins purified from Leishmania infantum plus saponin showed a specific production of IFN-γ, IL-12 and GM-CSF after in vitro stimulation with L. infantum ribosomal proteins. Vaccinated mice showed a reduction in the liver and spleen parasite burdens after L. chagasi infection. After L. amazonensis challenge, vaccinated mice showed a decrease of the dermal pathology and a reduction in the parasite loads in the footpad and spleen. In both models, protection was correlated to an IL-12-dependent production of IFN-γ by CD4(+) and CD8(+) T cells that activate macrophages for the synthesis of NO. In the protected mice a decrease in the parasite-mediated IL-4 and IL-10 responses was also observed. In mice challenged with L. amazonensis, lower levels of anti-parasite-specific antibodies were detected. Thus, Leishmania ribosomal proteins plus saponin fits the requirements to compose a pan-Leishmania vaccine.
恰加斯锥虫和亚马逊巴贝斯虫是南美的不同临床形式的人类利什曼病的病原体。为了筛选针对不同利什曼原虫物种的疫苗候选抗原,我们尝试用利什曼核糖体蛋白和皂苷作为佐剂对 BALB/c 小鼠进行疫苗接种,以抵抗两种寄生虫的挑战感染。用从婴儿利什曼原虫中纯化的寄生虫核糖体蛋白加皂苷接种的小鼠在体外用婴儿利什曼原虫核糖体蛋白刺激后表现出 IFN-γ、IL-12 和 GM-CSF 的特异性产生。感染恰加斯锥虫后,接种疫苗的小鼠肝脏和脾脏中的寄生虫负荷减少。在亚马逊巴贝斯虫感染后,接种疫苗的小鼠皮肤病理减少,足垫和脾脏中的寄生虫负荷减少。在这两种模型中,保护与 CD4(+)和 CD8(+)T 细胞产生的 IFN-γ的 IL-12 依赖性有关,这些细胞激活巨噬细胞合成 NO。在受保护的小鼠中,还观察到寄生虫介导的 IL-4 和 IL-10 反应的减少。在感染亚马逊巴贝斯虫的小鼠中,检测到较低水平的抗寄生虫特异性抗体。因此,利什曼核糖体蛋白加皂苷符合构成泛利什曼疫苗的要求。