Martins Vívian Tamietti, Lage Daniela Pagliara, Duarte Mariana Costa, Costa Lourena Emanuele, Garde Esther, Rodrigues Marcella Rezende, Chávez-Fumagalli Miguel Angel, Menezes-Souza Daniel, Roatt Bruno Mendes, Tavares Carlos Alberto Pereira, Soto Manuel, Coelho Eduardo Antonio Ferraz
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
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.
Acta Trop. 2016 Feb;154:73-81. doi: 10.1016/j.actatropica.2015.11.006. Epub 2015 Nov 21.
The present study aimed to evaluate a new Leishmania-specific hypothetical protein, LiHyT, as a vaccine candidate against VL. The immunogenicity of the recombinant protein (rLiHyT) plus saponin was evaluated in BALB/c mice. In the results, it is shown that rLiHyT plus saponin vaccinated mice produced high levels of IFN-γ, IL-12, and GM-CSF after in vitro stimulation of spleen cells using both rLiHyT and Leishmania infantum SLA. The protective efficacy was evaluated after subcutaneous challenge with stationary promastigotes of L. infantum. Immunized and infected mice, when compared to the controls, showed significant reductions in the number of parasites in the liver, spleen, bone marrow, and in the paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD4(+) T cells, with a minor contribution of CD8(+) T cells. In these mice, a decrease in the parasite-mediated IL-4 and IL-10 responses, as well as a predominance of LiHyT- and parasite-specific IgG2a isotype antibodies, were also observed. The present study showed that a new Leishmania-specific protein, when combined with a Th1-type adjuvant, presents potential to be used as a vaccine against VL.
本研究旨在评估一种新的利什曼原虫特异性假设蛋白LiHyT作为抗内脏利什曼病疫苗候选物的可能性。在BALB/c小鼠中评估了重组蛋白(rLiHyT)加皂苷的免疫原性。结果显示,用rLiHyT和婴儿利什曼原虫可溶性抗原(SLA)体外刺激脾细胞后,接种rLiHyT加皂苷的小鼠产生了高水平的干扰素-γ(IFN-γ)、白细胞介素-12(IL-12)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)。在用婴儿利什曼原虫静止前鞭毛体进行皮下攻击后评估了保护效力。与对照组相比,免疫并感染的小鼠在肝脏、脾脏、骨髓以及爪部引流淋巴结中的寄生虫数量显著减少。保护作用与主要由CD4(+) T细胞产生的依赖IL-12的IFN-γ生成有关,CD8(+) T细胞的贡献较小。在这些小鼠中,还观察到寄生虫介导的IL-4和IL-10反应减少,以及LiHyT和寄生虫特异性IgG2a同种型抗体占优势。本研究表明,一种新的利什曼原虫特异性蛋白与Th1型佐剂联合使用时,具有作为抗内脏利什曼病疫苗的潜力。