Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Departamento de Ciências Biológicas, Insituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Brazil.
Parasite Immunol. 2024 May;46(5):e13037. doi: 10.1111/pim.13037.
The treatment for visceral leishmaniasis (VL) causes toxicity in patients, entails high cost and/or leads to the emergence of resistant strains. No human vaccine exists, and diagnosis presents problems related to the sensitivity or specificity of the tests. Here, we tested two phage clones, B1 and D11, which were shown to be protective against Leishmania infantum infection in a murine model as immunotherapeutics to treat mice infected with this parasite species. The phages were used alone or with amphotericin B (AmpB), while other mice received saline, AmpB, a wild-type phage (WTP) or WTP/AmpB. Results showed that the B1/AmpB and D11/AmpB combinations induced polarised Th1-type cellular and humoral responses, which were primed by high levels of parasite-specific IFN-γ, IL-12, TNF-α, nitrite and IgG2a antibodies, which reflected in significant reductions in the parasite load in distinct organs of the animals when analyses were performed 1 and 30 days after the treatments. Reduced organic toxicity was also found in these animals, as compared with the controls. In conclusion, preliminary data suggest the potential of the B1/AmpB and D11/AmpB combinations as immunotherapeutics against L. infantum infection.
内脏利什曼病（VL）的治疗方法会导致患者产生毒性，费用高昂，而且会导致耐药菌株的出现。目前还没有人类疫苗，而诊断也存在与测试的敏感性或特异性相关的问题。在这里，我们测试了两种噬菌体克隆，B1 和 D11，它们在小鼠模型中被证明具有针对利什曼原虫感染的保护作用，可以作为免疫疗法来治疗感染这种寄生虫的小鼠。噬菌体单独使用或与两性霉素 B（AmpB）一起使用，而其他小鼠则接受生理盐水、AmpB、野生型噬菌体（WTP）或 WTP/AmpB。结果表明，B1/AmpB 和 D11/AmpB 组合诱导了极化的 Th1 型细胞和体液反应，这是由高水平的寄生虫特异性 IFN-γ、IL-12、TNF-α、亚硝酸盐和 IgG2a 抗体引发的，这些反应反映在治疗后 1 天和 30 天后对动物不同器官中的寄生虫负荷进行分析时，显著降低了寄生虫负荷。与对照组相比，这些动物的有机毒性也降低了。总之，初步数据表明 B1/AmpB 和 D11/AmpB 组合作为针对 L. infantum 感染的免疫疗法具有潜力。
