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从恰加斯婴儿利什曼原虫中提取的脂磷葡聚糖-3 蛋白加皂角苷佐剂:一种针对内脏利什曼病的新的有希望的疫苗。

Lipophosphoglycan-3 protein from Leishmania infantum chagasi plus saponin adjuvant: A new promising vaccine against visceral leishmaniasis.

机构信息

Department of General Biology, Federal University of Viçosa, MG, Brazil.

Department of General Biology, Federal University of Viçosa, MG, Brazil.

出版信息

Vaccine. 2021 Jan 8;39(2):282-291. doi: 10.1016/j.vaccine.2020.11.064. Epub 2020 Dec 11.

Abstract

Visceral leishmaniasis (VL) is a serious neglected tropical disease that affects humans and dogs in urban areas. There are no vaccines against human VL, and few licensed canine VL vaccines are currently available, which instigates the search for new antigens and vaccine formulations with prophylactic potential against VL in these hosts. In this study, we evaluated the immunization using the native and recombinant Leishmania infantum chagasi (L. chagasi) lipophosphoglycan-3 (LPG3) and the adjuvants saponin (SAP) and incomplete Freund adjuvant (IFA) against L. chagasi infection in BALB/c mice. The native LPG3 vaccine was immunogenic, inducing splenic IFN-γ and IL-10 production, and mixed Th1/Th2 response when associated with IFA. However, only mice vaccinated with LPG3-IFA presented a reduction in the splenic parasite load (96% in comparison to the PBS control group), but without a significant reduction in the hepatic parasitism. On the other hand, mice immunized with the LPG3-SAP vaccine presented a reduction of approximately 98% in both splenic and hepatic parasite load, accompanied by a Th1/Th17 response and IL-10 production by L. chagasi antigen (AgLc)-stimulated splenic cells. Importantly, vaccination with recombinant LPG3 (rLPG3)-SAP presented similar results to the native LPG3-SAP vaccine. Therefore, the rLPG3-SAP vaccine is qualified to be used in future tests in canine and human models, considering the technical and economic advantages of the recombinant protein production compared to the native protein and the results obtained in the murine model.

摘要

内脏利什曼病(VL)是一种严重的被忽视的热带病,影响城市地区的人和狗。目前还没有针对人类 VL 的疫苗,而目前可用的有许可证的犬 VL 疫苗也很少,这促使人们寻找针对这些宿主的具有预防 VL 潜力的新抗原和疫苗制剂。在这项研究中,我们评估了使用天然和重组利什曼原虫婴儿 Chagasi(L. chagasi)脂磷壁酸-3(LPG3)以及佐剂皂苷(SAP)和不完全弗氏佐剂(IFA)对 BALB/c 小鼠 L. chagasi 感染的免疫接种。天然 LPG3 疫苗具有免疫原性,可诱导脾 IFN-γ和 IL-10 的产生,并与 IFA 结合时产生混合 Th1/Th2 反应。然而,只有用 LPG3-IFA 接种的小鼠脾脏寄生虫负荷减少(与 PBS 对照组相比减少 96%),但肝寄生虫病没有显著减少。另一方面,用 LPG3-SAP 疫苗免疫的小鼠脾脏和肝脏寄生虫负荷均减少了约 98%,同时伴有 Th1/Th17 反应和 L. chagasi 抗原(AgLc)刺激的脾细胞产生 IL-10。重要的是,rLPG3-SAP 疫苗的接种效果与天然 LPG3-SAP 疫苗相似。因此,考虑到与天然蛋白相比,重组蛋白生产的技术和经济优势以及在鼠模型中获得的结果,rLPG3-SAP 疫苗有资格在犬和人类模型的未来测试中使用。

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