Cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination with subunit antigens.
Cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination with subunit antigens.
复制标题
用亚基抗原接种鼻内疫苗接种阳离子脂质体羟透明质酸杂交纳米颗粒。
DOI：
10.1016/j.jconrel.2015.04.010
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发表时间：
2015-06-28
期刊：
影响因子：
--
通讯作者：
Moon JJ
中科院分区：
文献类型：
--
作者：
Fan Y;Sahdev P;Ochyl LJ;Akerberg J;Moon JJ
在这里，我们报告了一种新的阳离子脂质体-透明质酸（HA）杂交纳米颗粒（NP）系统的开发，并利用模型抗原和鼠疫耶尔森菌的候选重组抗原F1-V，描述了这些纳米颗粒作为鼻内疫苗平台的特性。由DOTAP和DOPE组成的阳离子脂质体与阴离子HA生物聚合物的培养导致了高效的离子络合和均质脂质体-聚合物杂化NPs的形成，荧光共振能量转移、动态光散射和纳米颗粒跟踪分析证明了这一点。将阳离子脂质体与巯基羟基磷灰石结合，可以用巯基聚乙二醇对NPs进行表面修饰，从而形成DOTAP/HA核-聚乙二醇壳纳米结构。这些NPs被称为DOTAP-HA NPs，表现出更好的胶体稳定性和延长抗原释放时间。此外，用骨髓树突状细胞（bmdc）测量，DOTAP- ha NPs （LC50 ~ 0.4 mg/ml）显著降低了DOTAP脂质体（LC50 ~0.2 mg/ml）相关的细胞毒性至少20倍。此外，NPs与卵清蛋白（OVA）和分子佐剂单磷酰脂质a （MPLA）共负载，促进BMDC成熟和共刺激标记物（包括CD40、CD86和MHC-II）的上调，通过鼻内途径接种NPs的C57BL/6小鼠产生了强大的OVA特异性CD8+ T细胞和抗体反应。重要的是，与使用相同剂量的可溶性F1-V疫苗免疫的小鼠相比，鼻内接种含有F1-V和MPLA的NPs可诱导有效的体液免疫反应，免疫血清中F1-V特异性总IgG、IgG1和IgG2c滴度分别增加11倍、23倍和15倍，并诱导平衡的Th1/Th2体液免疫反应。总之，这些结果表明，脂质体-聚合物杂交NPs可能作为一种有前景的疫苗递送平台，用于鼻内接种鼠疫杆菌和其他感染性病原体。
Here we report the development of a new cationic liposome-hyaluronic acid (HA) hybrid nanoparticle (NP) system and present our characterization of these NPs as an intranasal vaccine platform using a model antigen and F1-V, a candidate recombinant antigen for Yersinia pestis, the causative agent of plague. Incubation of cationic liposomes composed of DOTAP and DOPE with anionic HA biopolymer led to efficient ionic complexation and formation of homogenous liposome-polymer hybrid NPs, as evidenced by fluorescence resonance energy transfer, dynamic light scattering, and nanoparticle tracking analyses. Incorporation of cationic liposomes with thiolated HA allowed for facile surface decoration of NPs with thiol-PEG, resulting in the formation of DOTAP/HA core-PEG shell nanostructures. These NPs, termed DOTAP-HA NPs, exhibited improved colloidal stability and prolonged antigen release. In addition, cytotoxicity associated with DOTAP liposomes (LC50 ~0.2 mg/ml) was significantly reduced by at least 20-fold with DOTAP-HA NPs (LC50 > 4 mg/ml), as measured with bone marrow dendritic cells (BMDCs). Furthermore, NPs co-loaded with ovalbumin (OVA) and a molecular adjuvant, monophosphoryl lipid A (MPLA) promoted BMDC maturation and upregulation of co-stimulatory markers, including CD40, CD86, and MHC-II, and C57BL/6 mice vaccinated with NPs via intranasal route generated robust OVA-specific CD8+ T cell and antibody responses. Importantly, intranasal vaccination with NPs co-loaded with F1-V and MPLA induced potent humoral immune responses with 11-, 23-, and 15-fold increases in F1-V-specific total IgG, IgG1, and IgG2c titers in immune sera by day 77, respectively, and induced balanced Th1/Th2 humoral immune responses, compared with the lack of sero-conversion in mice immunized with the equivalent doses of soluble F1-V vaccine. Overall, these results suggest that liposome-polymer hybrid NPs may serve as a promising vaccine delivery platform for intranasal vaccination against Y. pestis and other infectious pathogens.
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DOI：
10.3791/52771
发表时间：
2015-04-29
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Ochyl LJ;Moon JJ
通讯作者：
Moon JJ
影响因子：
3.1
作者：
Glynn, A;Roy, CJ;Clements, JD
通讯作者：
Clements, JD
影响因子：
6.1
作者：
Gong, Xing Wen;Wei, Dong Zhi;Xiong, Yu Chun
通讯作者：
Xiong, Yu Chun
影响因子：
5.5
作者：
Glynn, A;Freytag, LC;Clements, JD
通讯作者：
Clements, JD
影响因子：
2.2
作者：
Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G