Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses.
Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses.
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DOI：
10.1016/j.nano.2015.02.008
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Selvaraj P
中科院分区：
文献类型：
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作者：
Patel JM;Kim MC;Vartabedian VF;Lee YN;He S;Song JM;Choi HJ;Yamanaka S;Amaram N;Lukacher A;Montemagno CD;Compans RW;Kang SM;Selvaraj P
重组病毒样纳米颗粒（VLP）是一种很有前途的纳米颗粒平台，用于开发针对许多病毒的安全疫苗。在此，我们描述了一种新的和快速的蛋白质转移过程，以提高包膜VLP的效力，通过修饰流感病毒VLP与外源添加的糖基磷脂酰肌醇锚定的免疫刺激分子（GPI-ISMs）。在蛋白质转移的情况下，GPI-ISM掺入到VLP上的水平可通过改变孵育时间和添加的GPI-ISM浓度来控制。ISM掺入依赖于GPI锚的存在，并且当在4°C下储存时，掺入的蛋白质稳定且功能性至少4周。用GPI-粒细胞巨噬细胞集落刺激因子（GM-CSF）-修饰的VLP接种小鼠，与未修饰的VLP相比，诱导更强的抗体应答和更好的抗异源流感病毒攻击的保护。因此，VLP可以通过蛋白质转移富集ISM以增加免疫应答的效力和广度，这在开发针对广谱包膜病毒的有效的基于纳米颗粒的疫苗中具有意义。
Recombinant virus-like nanoparticles (VLPs) are a promising nanoparticle platform to develop safe vaccines for many viruses. Herein, we describe a novel and rapid protein transfer process to enhance the potency of enveloped VLPs by decorating influenza VLPs with exogenously added glycosylphosphatidylinositol-anchored immunostimulatory molecules (GPI-ISMs). With protein transfer, the level of GPI-ISM incorporation onto VLPs is controllable by varying incubation time and concentration of GPI-ISMs added. ISM incorporation was dependent upon the presence of a GPI-anchor and incorporated proteins were stable and functional for at least 4 weeks when stored at 4°C. Vaccinating mice with GPI-granulocyte macrophage colony-stimulating factor (GM-CSF)-incorporated-VLPs induced stronger antibody responses and better protection against a heterologous influenza virus challenge than unmodified VLPs. Thus, VLPs can be enriched with ISMs by protein transfer to increase the potency and breadth of the immune response, which has implications in developing effective nanoparticle-based vaccines against a broad spectrum of enveloped viruses.