Lage D P, Martins V T, Duarte M C, Garde E, Chávez-Fumagalli M A, Menezes-Souza D, Roatt B M, Tavares C A P, Soto M, Coelho E A F
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Parasite Immunol. 2015 Dec;37(12):646-56. doi: 10.1111/pim.12287.
In this work, the effect of vaccination of a newly described Leishmania infantum antigenic protein has been studied in BALB/c mice infected with this parasite species. The LiHyD protein was characterized after a proteomic screening performed with the sera from dogs suffering visceral leishmaniasis (VL). Its recombinant version was expressed, purified and administered to BALB/c mice in combination with saponin. As a result of vaccination and 10 weeks after challenge using an infective dose of L. infantum stationary promastigotes, vaccinated mice showed lower parasite burdens in different organs (liver, spleen, bone marrow and footpads' draining lymph nodes) than mice inoculated with the adjuvant alone or the vaccine diluent. Protected mice showed anti-Leishmania IgG2a antibodies and a predominant IL-12-driven IFN-γ production (mainly produced by CD4(+) T cells) against parasite proteins, whereas unprotected controls showed anti-Leishmania IgG1 antibodies and parasite-mediated IL-4 and IL-10 responses. Vaccinated mice showed an anti-LiHyD IgG2a humoral response, and their spleen cells were able to secrete LiHyD-specific IFN-γ, IL-12 and GM-CSF cytokines before and after infection. The protection was correlated with the Leishmania-specific production on nitric oxide. Altogether, the results indicate that the new LiHyD protein could be considered in vaccine formulations against VL.
在这项研究中,已对一种新描述的婴儿利什曼原虫抗原蛋白进行疫苗接种,研究其对感染该寄生虫物种的BALB/c小鼠的影响。LiHyD蛋白是在用患内脏利什曼病(VL)的犬只血清进行蛋白质组学筛选后鉴定出来的。其重组形式被表达、纯化,并与皂苷一起给予BALB/c小鼠。接种疫苗后,在用感染剂量的婴儿利什曼原虫静止前鞭毛体进行攻击10周后,接种疫苗的小鼠在不同器官(肝脏、脾脏、骨髓和足垫引流淋巴结)中的寄生虫负荷低于单独接种佐剂或疫苗稀释剂的小鼠。受到保护的小鼠表现出抗利什曼原虫IgG2a抗体以及针对寄生虫蛋白的主要由IL-12驱动的IFN-γ产生(主要由CD4(+) T细胞产生),而未受保护的对照组表现出抗利什曼原虫IgG1抗体以及寄生虫介导的IL-4和IL-10反应。接种疫苗的小鼠表现出抗LiHyD IgG2a体液反应,并且它们的脾细胞在感染前后都能够分泌LiHyD特异性的IFN-γ、IL-12和GM-CSF细胞因子。这种保护作用与利什曼原虫特异性一氧化氮的产生相关。总之,结果表明新的LiHyD蛋白可用于针对VL的疫苗制剂中。