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 Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Microb Pathog. 2021 Feb;151:104745. doi: 10.1016/j.micpath.2021.104745. Epub 2021 Jan 21.
Treatment for visceral leishmaniasis (VL) is hampered mainly by the toxicity and/or high cost of antileishmanial drugs. What is more, variability on sensitivity and/or specificity of diagnostic tests hinders effective disease management. In this context, prophylactic vaccination should be considered as a strategy to prevent disease. In the present study, immunogenicity of the Leishmania eukaryotic Elongation Factor-1 beta (EF1b) protein, classified as a Leishmania virulence factor, was evaluated in vitro and in vivo and tested, for the first time, as a vaccine candidate against Leishmania infantum infection. The antigen was administered as DNA vaccine or as recombinant protein (rEF1b) delivered in saponin. BALB/c mice immunization with a DNA plasmid and recombinant protein plus saponin induced development of specific Th1-type immunity, characterized by high levels of IFN-γ, IL-12, GM-CSF, both T cell subtypes and antileishmanial IgG2a isotype antibodies, before and after infection. This immunological response to the vaccines was corroborated further by parasitological analysis of the vaccinated and then challenged mice, which showed significant reductions in the parasite load in their liver, spleen, bone marrow and draining lymph nodes, when compared to the controls. Vaccination using rEF1b/saponin induced a more robust Th1 response and parasitological protection when compared to the DNA vaccine. Furthermore, in vitro analysis of lymphoproliferation, IFN-γ and IL-10 levels in human PBMC cultures showed as well development of a specific Th1-type response. In conclusion, data suggest that EF1b could be a promising vaccine candidate to protect against L. infantum infection.
内脏利什曼病(VL)的治疗主要受到抗利什曼原虫药物毒性和/或高成本的阻碍。更重要的是,诊断测试的敏感性和/或特异性的变化阻碍了有效的疾病管理。在这种情况下,预防性疫苗接种应被视为预防疾病的一种策略。在本研究中,对被归类为利什曼原虫毒力因子的真核延伸因子-1β(EF1b)蛋白的免疫原性进行了体外和体内评估,并首次作为针对利什曼原虫感染的候选疫苗进行了测试。该抗原作为 DNA 疫苗或重组蛋白(rEF1b)与皂苷联合给药。BALB/c 小鼠用 DNA 质粒和重组蛋白加皂苷免疫,在感染前后诱导产生了特异性 Th1 型免疫,其特征是高水平的 IFN-γ、IL-12、GM-CSF、两种 T 细胞亚型和抗利什曼原虫 IgG2a 同种型抗体。疫苗接种后对受感染和随后受到挑战的小鼠进行寄生虫学分析,进一步证实了这种免疫反应,与对照组相比,其肝脏、脾脏、骨髓和引流淋巴结中的寄生虫负荷显著降低。与 DNA 疫苗相比,rEF1b/皂苷疫苗诱导的 Th1 反应和寄生虫保护更为强烈。此外,体外分析人 PBMC 培养物中的淋巴增殖、IFN-γ和 IL-10 水平也显示出特异性 Th1 型反应的发展。总之,数据表明 EF1b 可能是一种有前途的疫苗候选物,可预防利什曼原虫感染。