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钩端螺旋体因子H结合蛋白作为多亚基疫苗对仓鼠钩端螺旋体病的作用:减少肾脏定植并增强保护

Reduced Renal Colonization and Enhanced Protection by Leptospiral Factor H Binding Proteins as a Multisubunit Vaccine Against Leptospirosis in Hamsters.

作者信息

Techawiwattanaboon Teerasit, Barnier-Quer Christophe, Palaga Tanapat, Jacquet Alain, Collin Nicolas, Sangjun Noppadon, Komanee Pat, Piboonpocanun Surapon, Patarakul Kanitha

机构信息

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.

Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine Research and Development, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.

出版信息

Vaccines (Basel). 2019 Aug 22;7(3):95. doi: 10.3390/vaccines7030095.

Abstract

Subunit vaccines conferring complete protection against leptospirosis are not currently available. The interactions of factor H binding proteins (FHBPs) on pathogenic leptospires and host factor H are crucial for immune evasion by inhibition of complement-mediated killing. The inhibition of these interactions may be a potential strategy to clear leptospires in the host. This study aimed to evaluate a multisubunit vaccine composed of four known leptospiral FHBPs: LigA domain 7-13 (LigAc), LenA, LcpA, and Lsa23, for its protective efficacy in hamsters. The mono and multisubunit vaccines formulated with LMQ adjuvant, a combination of neutral iposome, onophosphoryl lipid A, and fraction 21, induced high and comparable specific antibody (IgG) production against individual antigens. Hamsters immunized with the multisubunit vaccine showed 60% survival following the challenge by 20 LD of serovar Pomona. No significant difference in survival rate and pathological findings of target organs was observed after vaccinations with multisubunit or mono-LigAc vaccines. However, the multisubunit vaccine significantly reduced leptospiral burden in surviving hamsters in comparison with the monosubunit vaccines. Therefore, the multisubunit vaccine conferred partial protection and reduced renal colonization against virulence infection in hamsters. Our multisubunit formulation could represent a promising vaccine against leptospirosis.

摘要

目前尚无能够完全预防钩端螺旋体病的亚单位疫苗。致病性钩端螺旋体上的因子H结合蛋白(FHBPs)与宿主因子H的相互作用对于通过抑制补体介导的杀伤来逃避免疫至关重要。抑制这些相互作用可能是清除宿主体内钩端螺旋体的一种潜在策略。本研究旨在评估一种由四种已知的钩端螺旋体FHBPs组成的多亚单位疫苗:LigA结构域7-13(LigAc)、LenA、LcpA和Lsa23,在仓鼠中的保护效果。用LMQ佐剂(一种由中性脂质体、单磷酰脂质A和21组分组成的组合)配制的单亚单位和多亚单位疫苗诱导产生了针对单个抗原的高水平且相当的特异性抗体(IgG)。用多亚单位疫苗免疫的仓鼠在受到20个致死剂量的波摩那群攻击后,存活率为60%。接种多亚单位疫苗或单-LigAc疫苗后,存活率和靶器官的病理结果均未观察到显著差异。然而,与单亚单位疫苗相比,多亚单位疫苗显著降低了存活仓鼠体内的钩端螺旋体载量。因此,多亚单位疫苗在仓鼠中提供了部分保护,并减少了针对毒力感染的肾脏定植。我们的多亚单位制剂可能是一种有前景的钩端螺旋体病疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f64/6789851/f36b570730bf/vaccines-07-00095-g001a.jpg

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