Gold nanoparticle-M2e conjugate coformulated with CpG induces protective immunity against influenza A virus.
Gold nanoparticle-M2e conjugate coformulated with CpG induces protective immunity against influenza A virus.
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金纳米粒子-M2E与CPG共轭偶联物可诱导对流感病毒的保护性免疫。
DOI：
10.2217/nnm.13.58
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Gill HS
中科院分区：
文献类型：
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作者：
Tao W;Ziemer KS;Gill HS
本研究旨在通过将甲型流感病毒基质2蛋白（M2e）高度保守的胞外区域与金纳米粒子（AuNP）缀合来开发一种新型甲型流感疫苗，并在小鼠流感攻击模型中测试该疫苗。合成了柠檬酸盐还原的金纳米粒子（直径：12 nm），并通过透射电子显微镜和动态光散射进行了表征。 M2e 通过硫醇-金相互作用与 AuNP 缀合，形成 M2e-AuNP 缀合物。通过紫外-可见光谱证实了颗粒稳定性，并通过 X 射线光电子能谱进一步表征了 M2e 共轭。使用带有或不带有 CpG（富含胞嘧啶-鸟嘌呤的寡核苷酸）作为佐剂的 M2e-AuNP 和适当的对照组对小鼠进行免疫接种。收集血清并测量 M2e 特异性免疫球蛋白 (IgG)，并用 PR8-H1N1 流感病毒攻击免疫小鼠。 M2e 封端的 AuNP 可以冻干并稳定地重悬于水中。用 M2e-AuNP 缀合物对小鼠进行鼻内疫苗接种可诱导 M2e 特异性 IgG 血清抗体，在添加可溶性 CpG 作为佐剂后，该抗体显着增加。在受到致死性 PR8 攻击后，接种 M2e-AuNP 缀合物的小鼠仅受到部分保护，而除了 M2e-AuNP 之外还接受可溶性 CpG 作为佐剂的小鼠则受到完全保护。总体而言，这项研究证明了使用 M2e-AuNP 缀合物与 CpG 作为佐剂作为开发甲型流感疫苗的平台的潜力。
This study aimed to develop a novel influenza A vaccine by conjugating the highly conserved extracellular region of the matrix 2 protein (M2e) of influenza A virus to gold nanoparticles (AuNPs) and to test the vaccine in a mouse influenza challenge model. Citrate-reduced AuNPs (diameter: 12 nm) were synthesized, and characterized by transmission electron microscopy and dynamic light scattering. M2e was conjugated to AuNPs through thiol–gold interactions to form M2e–AuNP conjugates. Particle stability was confirmed by UV–visible spectra, and M2e conjugation was further characterized by x-ray photoelectron spectroscopy. Mice were immunized with M2e–AuNPs with or without CpG (cytosine-guanine rich oligonucleotide) as an adjuvant with appropriate control groups. Sera was collected and M2e-specific immunoglobulin (IgG) was measured, and immunized mice were challenged with PR8-H1N1 influenza virus. M2e-capped AuNPs could be lyophilized and stably resuspended in water. Intranasal vaccination of mice with M2e–AuNP conjugates induced M2e-specific IgG serum antibodies, which significantly increased upon addition of soluble CpG as adjuvant. Upon challenge with lethal PR8, mice vaccinated with M2e-AuNP conjugates were only partially protected, while mice that received soluble CpG as adjuvant in addition to M2e–AuNP were fully protected. Overall, this study demonstrates the potential of using the M2e–AuNP conjugates with CpG as an adjuvant as a platform for developing an influenza A vaccine.