摘要
背景:在过去的几年里,DNA疫苗的免疫原性已经通过使用共刺激分子和分子佐剂来优化。据报道,包含炭疽毒素受体-1(ANTXR-1,别名TEM8,肿瘤内皮标记物8)的血管性血友病A(vWA / A)结构域的DNA序列的质粒(pATRex)佐剂通过诱导不溶性细胞内聚集体的形成。显然,由于聚集体形成促使小鼠骨质减少,我们面临着关于pATRex作为佐剂的安全性的不安的发现。 目的:本研究提供了关于骨髓内蛋白质佐剂作用的进一步证据,并对自身聚集蛋白佐剂对骨髓龛的免疫毒性提出质疑。 方法和结果:使用组织学,生物化学和蛋白质组学分析,我们阐明了骨髓龛内的pATRex效应,特别是我们证明细胞因子/趋化因子产生被破坏的再生障碍性样骨髓。 结论:上述发现为基于编码蛋白质聚集域的质粒的佐剂破坏骨髓元件的生理学特征提供了有力的支持。
关键词: 骨髓,骨髓龛,骨质减少症,DNA疫苗,佐剂,蛋白质聚集体。
Current Gene Therapy
Title:Molecular Adjuvants Based on Plasmids Encoding Protein Aggregation Domains Affect Bone Marrow Niche Homeostasis
Volume: 17 Issue: 5
关键词: 骨髓,骨髓龛,骨质减少症,DNA疫苗,佐剂,蛋白质聚集体。
摘要: Background: During last years, DNA vaccine immunogenicity has been optimized by the employment of co-stimulatory molecules and molecular adjuvants. It has been reported that plasmid (pATRex), encompassing the DNA sequence for the von Willebrand A (vWA/A) domain of the Anthrax Toxin Receptor-1 (ANTXR-1, alias TEM8, Tumor Endothelial Marker 8), acts as strong immune adjuvant by inducing formation of insoluble intracellular aggregates. Markedly, we faced with upsetting findings regarding the safety of pATRex as adjuvant since the aggregosome formation prompted to osteopenia in mice.
Objective: The present study provides additional evidences about the proteinaceous adjuvants action within bone marrow and questioned regarding the self-aggregation protein adjuvants immunotoxicity on marrow niches.
Methods & Results: Using histological, biochemical and proteomic assays we shed light on pATRex effects within bone marrow niche and specifically we evidenced an aplastic-like bone marrow with disrupted cytokine/chemokine production.
Conclusion: The above findings provide compelling support to the thesis that adjuvants based on plasmids encoding protein aggregation domains disrupt the physiological features of the bone marrow elements.
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Cite this article as:
Molecular Adjuvants Based on Plasmids Encoding Protein Aggregation Domains Affect Bone Marrow Niche Homeostasis, Current Gene Therapy 2017; 17 (5) . https://dx.doi.org/10.2174/1566523218666180105122626
DOI https://dx.doi.org/10.2174/1566523218666180105122626 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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