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A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis

机译：用于分枝杆菌的肽的疫苗用于分析副肢体分析

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Recent efforts to develop a live attenuated vaccine against Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of Johne's disease (JD), revealed relA is important in Map virulence. Deletion of the relA gene impairs the ability of Map to establish a persistent infection. Analysis of the basis for this observation revealed infection with a relA deletion mutant (Delta relA) elicits development of cytotoxic CD8 T cells (CTL) with the ability to kill intracellular bacteria. Further analysis of the recall response elicited by Delta relA vaccination showed a 35 kDa membrane peptide (MMP) is one of the targets of the immune response, suggesting it might be possible to develop a peptide-based vaccine based on MMP. To explore this possibility, ex vivo vaccination studies were conducted with MMP alone and incorporated into a nanoparticle (NP) vector comprised of poly (D, L-lactide-co-glycolide) and monophosphoryl lipid A (PLGA/MPLA). As reported, ex vivo vaccination studies showed CD8 CTL were elicited with classic and monocyte derived dendritic cells (cDC and MoDC) pulsed with MMP alone and incorporated into a PGLA/MPLA vector. Incorporation of MMP into a NP vector enhanced the ability of CD8 CTL to kill intracellular bacteria. The findings indicate incorporation of MMP into a PGLAIMPLA nanoparticle vector is one of the possible ways to develop a MMP based vaccine for Johne's disease. (C) 2019 Elsevier Ltd. All rights reserved.
机译：最近努力开发针对分枝杆菌患者的活病毒疫苗。伞菌（MAP），Johne病（JD）的致病剂，揭示了Rela在地图毒力中很重要。缺失rela基因损害地图建立持续感染的能力。分析该观察结果的基础揭示了rela缺失突变体（Delta Rela）的感染引发细胞毒性CD8 T细胞（CTL）的发育，具有杀死细胞内细菌的能力。进一步分析ΔReaRA疫苗接种引发的召回响应显示35kDa膜肽（MMP）是免疫应答的靶标的一种，表明它可能是基于MMP的基于肽的疫苗。为了探讨这种可能性，通过单独使用MMP进行前体内疫苗接种研究，并掺入包含聚（D，L-丙交酯 - 共乙酰化）和单磷虾脂质A（PLGA / MPLA）的纳米颗粒（NP）载体中。如报道，以单独用MMP脉冲的经典和单核细胞衍生的树突细胞（CDC和MODC）引发CD8 CTL，并掺入PGLA / MPLA载体中。将MMP掺入NP载体增强CD8 CTL杀死细胞内细菌的能力。结果表明MMP掺入PGlaimpla纳米颗粒载体中，是开发Johne病的MMP疫苗的可能方法之一。 （c）2019 Elsevier Ltd.保留所有权利。

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