Plant viral nanoparticles-based HER2 vaccine: Immune response influenced by differential transport, localization and cellular interactions of particulate carriers
Plant viral nanoparticles-based HER2 vaccine: Immune response influenced by differential transport, localization and cellular interactions of particulate carriers
复制标题
DOI：
10.1016/j.biomaterials.2016.12.030
复制
发表时间：
2017-03-01
期刊：
影响因子：
14
通讯作者：
Steinmetz, Nicole F.
中科院分区：
文献类型：
--
作者：
Shukla, Sourabh;Myers, Jay T.;Steinmetz, Nicole F.
癌症疫苗旨在引起内源性适应性免疫反应，能够成功识别和消除残留或复发的肿瘤。这种方法可以通过产生长期的治疗效果和免疫记忆，同时限制全身毒性，从而潜在地克服被动免疫疗法的缺点。疫苗有效性的一个关键决定因素是肿瘤相关抗原向专业抗原呈递细胞（APCs）的有效运输和递送。植物病毒纳米颗粒（VNPs）具有对APCs的天然趋向性和高载荷承载能力，可能是特别有效的疫苗载体。VNP平台技术的适用性取决于严格的结构-功能关系。我们比较了两种不同的VNP平台：二十面体豇豆花叶病毒（CPMV）和丝状马铃薯病毒X （PVX）。具体来说，我们评估了传递人表皮生长因子受体2（HER2）表位的工程化VNPs在体内治疗和预防HER2（+）恶性肿瘤的能力。我们的研究结果证实了二十面体CPMV颗粒的结构-功能关系，与丝状PVX颗粒相比，CPMV颗粒的淋巴结运输和保留显著增强，apc的摄取/激活也更大。这些增强的免疫细胞相互作用和运输特性导致CPMV-vs提高了her2特异性抗体滴度。基于pvx的肽疫苗。“合成病毒学”领域正在迅速扩大，许多平台正在开发和临床前测试；我们的研究强调，在肽疫苗展示技术的背景下，需要进行系统的研究，以确定指导设计和合理选择平台的规则。(C) 2016 Elsevier Ltd.版权所有。
Cancer vaccines are designed to elicit an endogenous adaptive immune response that can successfully recognize and eliminate residual or recurring tumors. Such approaches can potentially overcome shortcomings of passive immunotherapies by generating long-lived therapeutic effects and immune memory while limiting systemic toxicities. A critical determinant of vaccine efficacy is efficient transport and delivery of tumor-associated antigens to professional antigen presenting cells (APCs). Plant viral nanoparticles (VNPs) with natural tropism for APCs and a high payload carrying capacity may be particularly effective vaccine carriers. The applicability of VNP platform technologies is governed by stringent structure-function relationships. We compare two distinct VNP platforms: icosahedral cowpea mosaic virus (CPMV) and filamentous potato virus X (PVX). Specifically, we evaluate in vivo capabilities of engineered VNPs delivering human epidermal growth factor receptor 2 (HER2) epitopes for therapy and prophylaxis of HER2(+) malignancies. Our results corroborate the structure-function relationship where icosahedral CPMV particles showed significantly enhanced lymph node transport and retention, and greater uptake by/activation of APCs compared to filamentous PVX particles. These enhanced immune cell interactions and transport properties resulted in elevated HER2-specific antibody titers raised by CPMV-vs. PVX-based peptide vaccine. The 'synthetic virology' field is rapidly expanding with numerous platforms undergoing development and preclinical testing; our studies highlight the need for systematic studies to define rules guiding the design and rational choice of platform, in the context of peptide vaccine display technologies. (C) 2016 Elsevier Ltd. All rights reserved.