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评价使用重组 LigA 和 LigB 嵌合体针对钩端螺旋体病诱导保护性免疫应答的不同策略。

Evaluation of different strategies to promote a protective immune response against leptospirosis using a recombinant LigA and LigB chimera.

机构信息

Biotecnologia, Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Brazil.

Biotecnologia, Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Brazil.

出版信息

Vaccine. 2019 Mar 22;37(13):1844-1852. doi: 10.1016/j.vaccine.2019.02.010. Epub 2019 Feb 28.

Abstract

Leptospirosis is a zoonosis of worldwide distribution, caused by infection with pathogenic Leptospira species. The vaccines that are currently available are bacterins, with limited human use, that confer short-term, serovar-specific immunity. Lig proteins are considered to be the best vaccine candidates to date. Here, we aimed to construct a recombinant Lig chimera (LC) comprised of LigAni and LigBrep fragments, and to evaluate it as subunit or DNA vaccine using different administration strategies. Vaccines were formulated with 50 µg of recombinant LC associated with different adjuvants or with 100 µg of pTARGET/LC. Four-week-old hamsters received two doses of vaccine with different strategies and were challenged with 5 × DLLeptospira interrogans serovar Copenhageni strain Fiocruz L1-130. The immune response generated by Lig chimera conferred 100% protection to hamsters treated with at least one dose of recombinant LC. Despite the high levels of antibodies that vaccinated animals produced, a sterilizing immunity was not achieved. The lack of a sterilizing immunity could indicate the importance of a mixed humoral and cellular immune response. The present study generated insights that will be useful in the future development of improved subunit vaccines against leptospirosis.

摘要

钩端螺旋体病是一种分布广泛的人畜共患病,由致病性钩端螺旋体感染引起。目前可用的疫苗是菌苗,其人类应用有限,只能提供短期、血清型特异性免疫。Lig 蛋白被认为是迄今为止最好的疫苗候选物。在这里,我们旨在构建由 LigAni 和 LigBrep 片段组成的重组 Lig 嵌合体(LC),并使用不同的给药策略将其作为亚单位或 DNA 疫苗进行评估。疫苗用 50μg 重组 LC 与不同佐剂或 100μg pTARGET/LC 联合配制。4 周龄的仓鼠接受两种不同策略的疫苗接种,并接受 5×DLLeptospira interrogans 血清型 Copenhageni 菌株 Fiocruz L1-130 的攻击。用至少一剂重组 LC 治疗的仓鼠产生的 Lig 嵌合体免疫应答可提供 100%的保护。尽管接种疫苗的动物产生了高水平的抗体,但并未实现杀菌性免疫。缺乏杀菌性免疫可能表明体液和细胞免疫应答的混合很重要。本研究为未来开发针对钩端螺旋体病的改良亚单位疫苗提供了有用的见解。

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