Martínez-Rodrigo Abel, Mas Alicia, Álvarez-Campos Daniel, Orden José A, Domínguez-Bernal Gustavo, Carrión Javier
INMIVET, Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense Madrid, 28040 Madrid, Spain.
Vaccines (Basel). 2020 Jul 1;8(3):352. doi: 10.3390/vaccines8030352.
Visceral leishmaniosis (VL) caused by is a disease with an increasing prevalence worldwide. Treatments are expensive, toxic, and ineffective. Therefore, vaccination seems to be a promising approach to control VL. Peptide-based vaccination is a useful method due to its stability, absence of local side effects, and ease of scaling up. In this context, bioinformatics seems to facilitate the use of peptides, as this analysis can predict high binding affinity epitopes to MHC class I and II molecules of different species. We have recently reported the use of HisAK70 DNA immunization in mice to induce a resistant phenotype against , , and infections. In the present study, we used bioinformatics tools to select promising multiepitope peptides (HisDTC and AK) from the polyprotein encoded in the HisAK70 DNA to evaluate their immunogenicity in the murine model of VL by . Our results revealed that both multiepitope peptides were able to induce the control of VL in mice. Furthermore, HisDTC was able to induce a better cell-mediated immune response in terms of reduced parasite burden, protective cytokine profile, leishmanicidal enzyme modulation, and specific IgG2a isotype production in immunized mice, before and after infectious challenge. Overall, this study indicates that the HisDTC chimera may be considered a satisfactory tool to control VL because it is able to activate a potent CD4 and CD8 T-cell protective immune responses.
由[病原体名称未给出]引起的内脏利什曼病(VL)在全球范围内的患病率呈上升趋势。治疗方法昂贵、有毒且无效。因此,疫苗接种似乎是控制VL的一种有前景的方法。基于肽的疫苗接种是一种有用的方法,因为它具有稳定性、无局部副作用且易于扩大规模。在这种情况下,生物信息学似乎有助于肽的使用,因为这种分析可以预测不同物种的MHC I类和II类分子的高结合亲和力表位。我们最近报道了在小鼠中使用HisAK70 DNA免疫来诱导针对[病原体名称未给出]、[病原体名称未给出]和[病原体名称未给出]感染的抗性表型。在本研究中,我们使用生物信息学工具从HisAK70 DNA编码的多蛋白中选择有前景的多表位肽(HisDTC和AK),以通过[具体方法未给出]评估它们在VL小鼠模型中的免疫原性。我们的结果表明,两种多表位肽都能够在小鼠中诱导对VL的控制。此外,在感染攻击前后,HisDTC在降低寄生虫负荷、保护性细胞因子谱、利什曼杀伤酶调节以及免疫小鼠中特异性IgG2a同种型产生方面能够诱导更好的细胞介导免疫反应。总体而言,这项研究表明HisDTC嵌合体可能被认为是控制VL的一种令人满意的工具,因为它能够激活强大的CD4和CD8 T细胞保护性免疫反应。