噬菌体展示法筛选出的拟态物与两性霉素 B相结合的免疫疗法对治疗内脏利什曼病有效

IF 1.4 4区 医学 Q4 IMMUNOLOGY Parasite Immunology Pub Date : 2024-05-01 DOI:10.1111/pim.13037
Tauane Gonçalves Soyer, Raquel Soares Bandeira Câmara, Isabela Amorim Gonçalves Pereira, Fernanda Fonseca Ramos, Marcelo Moreira de Jesus, Fernanda Ludolf, Guilherme de Paula Costa, Daniela Pagliara Lage, Camila Simões de Freitas, Danniele Luciana Vale, Breno Luiz Pimenta, Vívian Tamietti Martins, Alexsandro Sobreira Galdino, Miguel Angel Chávez-Fumagalli, Bruno Mendes Roatt, Grasiele de Sousa Vieira Tavares, Eduardo Antonio Ferraz Coelho
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引用次数: 0

摘要

内脏利什曼病(VL)的治疗会给患者带来毒性、高昂的费用和/或导致耐药菌株的出现。目前还没有人用疫苗,诊断也存在检测灵敏度或特异性方面的问题。在这里,我们测试了两种噬菌体克隆(B1 和 D11),它们在小鼠模型中对幼年利什曼原虫感染具有保护作用,可作为免疫疗法治疗感染这种寄生虫的小鼠。这些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,这些反应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,在治疗后 1 天和 30 天进行分析时,动物不同器官中的寄生虫数量显著减少。与对照组相比,这些动物体内的有机物毒性也有所降低。总之,初步数据表明,B1/AmpB 和 D11/AmpB 组合具有作为抗幼虫感染免疫疗法的潜力。
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Immunotherapy Combining Mimotopes Selected by Phage Display Plus Amphotericin B Is Effective for Treatment Against Visceral Leishmaniasis.

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.

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来源期刊
Parasite Immunology
Parasite Immunology 医学-寄生虫学
CiteScore
4.70
自引率
4.50%
发文量
61
审稿时长
6-12 weeks
期刊介绍: Parasite Immunology is an international journal devoted to research on all aspects of parasite immunology in human and animal hosts. Emphasis has been placed on how hosts control parasites, and the immunopathological reactions which take place in the course of parasitic infections. The Journal welcomes original work on all parasites, particularly human parasitology, helminths, protozoa and ectoparasites.
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