Martins Vívian T, Lage Daniela P, Duarte Mariana C, Carvalho Ana Maria R S, Costa Lourena E, Mendes Tiago A O, Vale Danniele L, Menezes-Souza Daniel, Roatt Bruno M, Tavares Carlos A P, Soto Manuel, Coelho Eduardo A F
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil; Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
Cell Immunol. 2017 Mar;313:32-42. doi: 10.1016/j.cellimm.2016.12.008. Epub 2016 Dec 28.
Tegumentary leishmaniasis (TL) constitutes a major public health problem with significant morbidity worldwide. Synthetic peptide-based vaccines are attractive candidates to protect against leishmaniasis, since T cell-specific epitopes can be delivery to antigen-presenting cells, leading to the generation of a Th1 cell-mediated immunity. In this context, the present study aims to evaluate the immunogenicity and protective efficacy of a vaccine composed of major histocompatibility complex class I and II-restricted epitopes derived from four Leishmania infantum proteins to protect mice against Leishmania amazonensis infection. This recombinant fusion protein was administered in BALB/c mice alone or with saponin. As controls, animals received saline or saponin. In the results, the administration of the recombinant protein plus saponin induced a specific IFN-γ, IL-12 and GM-CSF production, as well as high IgG2a isotype antibody levels, which protected mice against a challenge using L. amazonensis promastigotes. Lower parasite burden was found in the infected footpads, liver, spleen and draining lymph node of vaccinated mice, when compared to those from the control groups. In addition, protection was associated with a lower IL-4 and IL-10 response, which was accompanied by the antileishmanial nitrite production by spleen cells of the animals. Interestingly, the recombinant protein administered alone induced a partial protection against challenge. In conclusion, this study shows a new vaccine candidate based on T cell-specific epitopes that was able to induce protection against L. amazonensis infection.
皮肤利什曼病（TL）是一个重大的公共卫生问题，在全球范围内导致大量发病。基于合成肽的疫苗是预防利什曼病的有吸引力的候选疫苗，因为T细胞特异性表位可以递送至抗原呈递细胞，从而产生Th1细胞介导的免疫。在此背景下，本研究旨在评估一种由来自四种婴儿利什曼原虫蛋白的主要组织相容性复合体I类和II类限制性表位组成的疫苗的免疫原性和保护效力，以保护小鼠免受亚马逊利什曼原虫感染。这种重组融合蛋白单独或与皂苷一起给予BALB/c小鼠。作为对照，动物接受生理盐水或皂苷。结果显示，重组蛋白加皂苷的给药诱导了特异性IFN-γ、IL-12和GM-CSF的产生，以及高IgG2a同种型抗体水平，这保护小鼠免受亚马逊利什曼原虫前鞭毛体的攻击。与对照组相比，接种疫苗小鼠的感染足垫、肝脏、脾脏和引流淋巴结中的寄生虫负荷较低。此外，保护作用与较低的IL-4和IL-10反应相关，同时动物脾脏细胞产生抗利什曼原虫亚硝酸盐。有趣的是，单独给予重组蛋白可诱导对攻击的部分保护。总之，本研究展示了一种基于T细胞特异性表位的新型候选疫苗，该疫苗能够诱导对亚马逊利什曼原虫感染的保护作用。
