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李斯特菌病中的细胞疫苗:李斯特菌抗原甘油醛-3-磷酸脱氢酶的作用

Cellular vaccines in listeriosis: role of the Listeria antigen GAPDH.

作者信息

Calderón-González Ricardo, Frande-Cabanes Elisabet, Bronchalo-Vicente Lucía, Lecea-Cuello M Jesús, Pareja Eduardo, Bosch-Martínez Alexandre, Fanarraga Mónica L, Yañez-Díaz Sonsoles, Carrasco-Marín Eugenio, Alvarez-Domínguez Carmen

机构信息

Grupo de Genómica, Proteómica y Vacunas, Primera Planta-Laboratorio 124, Fundación Marqués de Valdecilla-IFIMAV Santander, Spain ; Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria Santander, Spain.

Grupo de Genómica, Proteómica y Vacunas, Primera Planta-Laboratorio 124, Fundación Marqués de Valdecilla-IFIMAV Santander, Spain.

出版信息

Front Cell Infect Microbiol. 2014 Feb 21;4:22. doi: 10.3389/fcimb.2014.00022. eCollection 2014.

Abstract

The use of live Listeria-based vaccines carries serious difficulties when administrated to immunocompromised individuals. However, cellular carriers have the advantage of inducing multivalent innate immunity as well as cell-mediated immune responses, constituting novel and secure vaccine strategies in listeriosis. Here, we compare the protective efficacy of dendritic cells (DCs) and macrophages and their safety. We examined the immune response of these vaccine vectors using two Listeria antigens, listeriolysin O (LLO) and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), and several epitopes such as the LLO peptides, LLO189-201 and LLO91-99 and the GAPDH peptide, GAPDH1-22. We discarded macrophages as safe vaccine vectors because they show anti-Listeria protection but also high cytotoxicity. DCs loaded with GAPDH1-22 peptide conferred higher protection and security against listeriosis than the widely explored LLO91-99 peptide. Anti-Listeria protection was related to the changes in DC maturation caused by these epitopes, with high production of interleukin-12 as well as significant levels of other Th1 cytokines such as monocyte chemotactic protein-1, tumor necrosis factor-α, and interferon-γ, and with the induction of GAPDH1-22-specific CD4(+) and CD8(+) immune responses. This is believed to be the first study to explore the use of a novel GAPDH antigen as a potential DC-based vaccine candidate for listeriosis, whose efficiency appears to highlight the relevance of vaccine designs containing multiple CD4(+) and CD8(+) epitopes.

摘要

给免疫功能低下的个体接种基于活李斯特菌的疫苗存在严重困难。然而,细胞载体具有诱导多价天然免疫以及细胞介导免疫反应的优势,构成了针对李斯特菌病的新型安全疫苗策略。在此,我们比较树突状细胞(DCs)和巨噬细胞的保护效力及其安全性。我们使用两种李斯特菌抗原,即李斯特菌溶血素O(LLO)和甘油醛-3-磷酸脱氢酶(GAPDH)以及几种表位,如LLO肽、LLO189-201和LLO91-99以及GAPDH肽GAPDH1-22,来检测这些疫苗载体的免疫反应。我们摒弃巨噬细胞作为安全的疫苗载体,因为它们虽显示出抗李斯特菌保护作用,但也具有高细胞毒性。负载GAPDH1-22肽的DCs比广泛研究的LLO91-99肽对李斯特菌病具有更高的保护作用和安全性。抗李斯特菌保护作用与这些表位引起的DC成熟变化相关,包括白细胞介素-12的高产量以及其他Th1细胞因子如单核细胞趋化蛋白-1、肿瘤坏死因子-α和干扰素-γ的显著水平,以及GAPDH1-22特异性CD4(+)和CD8(+)免疫反应的诱导。据信这是第一项探索将新型GAPDH抗原用作针对李斯特菌病潜在的基于DC的疫苗候选物的研究,其效率似乎突出了包含多个CD4(+)和CD8(+)表位的疫苗设计的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f5/3930854/2dbf569a54a4/fcimb-04-00022-g0001.jpg

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