Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity.
Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity.
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DOI：
10.3390/pharmaceutics13101569
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发表时间：
2021-09-27
期刊：
影响因子：
5.4
通讯作者：
Lai PS
中科院分区：
文献类型：
--
作者：
Lin CA;Ho HM;Venkatesan P;Huang CY;Cheng YJ;Lin YH;Lin HY;Chen TY;Huang MH;Lai PS
近年来，药物/疫苗配方中常用的亲水性分子聚乙二醇赋形剂引起过敏反应的临床案例引起了人们的极大关注。为了开发无聚乙二醇佐剂，我们研究了以透明质酸-甘氨酸胆固醇(HACH)结合物形式存在的人体天然成分作为疫苗赋形剂的可行性。有趣的是，接枝了~13wt.%胆固醇的HACH具有良好的水分散性，可以作为乳化剂稳定角鲨烯/水界面，通过高剪切微流化器后得到乳白色的各向同性乳液(SQ@HACH)。结果表明，SQ@HACH颗粒的动态光散射法测得其单峰平均水动力直径约为190 nm，在4℃和37℃下存放20周以上具有良好的稳定性。以卵清蛋白(OVA)为抗原的小鼠模型免疫原性实验结果表明，SQ@HACH能显著增强抗原特异性免疫应答，包括抗体极化、T细胞细胞因子分泌和细胞毒性T淋巴细胞(CTL)激活。此外，与AlPO4相比，SQ@HACH在体内肌肉注射后表现出更低的局部炎症和快速吸收特性，表明HA衍生的结合物作为辅料在疫苗配方中具有潜在的功能，以增强T细胞介导的免疫。
Clinical cases of allergic reaction that are due to excipients containing polyethylene glycol (PEG), a hydrophilic molecule commonly used in drug/vaccine formulations, has attracted much attention in recent years. In order to develop PEG-free adjuvants, we investigated the feasibility of natural ingredients in the human body such as hyaluronic acid in the form of hyaluronic acid-glycine cholesterol (HACH) conjugate as an excipient for vaccine formulation. Interestingly, HACH grafted with ~13 wt.% cholesterol has good water dispersity and can serve as an emulsifier to stabilize the squalene/water interfaces, yielding a milky white and isotropic emulsion (SQ@HACH) after being passed through a high-shear microfluidizer. Our results show that SQ@HACH particles possessed a unimodal average hydrodynamic diameter of approximately 190 nm measured by dynamic light scattering and exhibited good stability upon storage at 4 °C and 37 °C for over 20 weeks. The results of immunogenicity using a mouse model with ovalbumin (OVA) as the antigen revealed that SQ@HACH significantly enhanced antigen-specific immune responses, including the polarization of IgG antibodies, the cytokine secretions of T cells, and enhancement of cytotoxic T lymphocyte (CTL) activation. Moreover, SQ@HACH revealed lower local inflammation and rapidly absorbing properties compared with AlPO4 after intramuscular injection in vivo, indicating the potential functions of the HA-derived conjugate as an excipient in vaccine formulations for enhancement of T cell-mediated immunity.
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影响因子：
5.5
作者：
Fieber, Wolfgang;Herrmann, Andreas;Sommer, Horst
通讯作者：
Sommer, Horst
影响因子：
3
作者：
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通讯作者：
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影响因子：
5.1
作者：
AL-Deen, F. M. Nawwab;Selomulya, C.;Plebanski, M.
通讯作者：
Plebanski, M.
DOI：
10.1016/b978-0-12-817778-5.00007-5
发表时间：
2020-01-17
期刊：
Nanopharmaceuticals
影响因子：
--
作者：
Diaz-Arévalo D;Zeng M
通讯作者：
Zeng M
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影响因子：
24.1
作者：
Fang, Hongliang;Ang, Bing;Wan, Tao
通讯作者：
Wan, Tao