Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
Department of Diagnostic Radiology, Dalhousie University, Halifax, NS, Canada.
J Biomed Sci. 2018 Jan 27;25(1):7. doi: 10.1186/s12929-018-0413-9.
Oil emulsions are commonly used as vaccine delivery platforms to facilitate slow release of antigen by forming a depot at the injection site. Antigen is trapped in the aqueous phase and as the emulsion degrades in vivo the antigen is passively released. DepoVax™ is a unique oil based delivery system that directly suspends the vaccine components in the oil diluent that forces immune cells to actively take up components from the formulation in the absence of passive release. The aim of this study was to use magnetic resonance imaging (MRI) with additional biological markers to evaluate and understand differences in clearance between several different delivery systems used in peptide-based cancer vaccines.
C57BL/6 mice were implanted with a cervical cancer model and vaccinated 5 days post-implant with either DepoVax (DPX), a water-in-oil emulsion (w/o), a squalene oil-in-water emulsion (squal o/w) or a saponin/liposome emulsion (sap/lip) containing iron oxide-labeled targeted antigen. MRI was then used to monitor antigen clearance, the site of injection, tumour and inguinal lymph node volumes and other gross anatomical changes. HLA-A2 transgenic mice were also vaccinated to evaluate immune responses of human directed peptides.
We demonstrated differences in antigen clearance between DPX and w/o both in regard to how quickly the antigen was cleared and the pattern in which it was cleared. We also found differences in lymph node responses between DPX and both squal o/w and sap/lip.
These studies underline the unique mechanism of action of this clinical stage vaccine delivery system.
油乳剂通常被用作疫苗传递平台,通过在注射部位形成储存库来促进抗原的缓慢释放。抗原被困在水相中,随着乳剂在体内降解,抗原被被动释放。DepoVax™ 是一种独特的油基传递系统,它将疫苗成分直接悬浮在油稀释剂中,迫使免疫细胞在没有被动释放的情况下主动从制剂中摄取成分。本研究的目的是使用磁共振成像 (MRI) 结合额外的生物标志物来评估和理解几种不同的肽类癌症疫苗传递系统之间的清除差异。
C57BL/6 小鼠植入宫颈癌模型,在植入后 5 天用 DepoVax (DPX)、水包油乳剂 (w/o)、角鲨烯油包水乳剂 (squal o/w) 或含有氧化铁标记的靶向抗原的皂苷/脂质体乳剂 (sap/lip) 进行疫苗接种。然后使用 MRI 监测抗原清除、注射部位、肿瘤和腹股沟淋巴结体积以及其他大体解剖变化。还使用 HLA-A2 转基因小鼠进行疫苗接种,以评估针对人类的肽的免疫反应。
我们证明了 DPX 和 w/o 之间在抗原清除速度和清除模式方面的差异。我们还发现 DPX 和 squal o/w 以及 sap/lip 之间在淋巴结反应方面存在差异。
这些研究强调了这种临床阶段疫苗传递系统的独特作用机制。