Fatty Acid-Mimetic Micelles for Dual Delivery of Antigens and Imidazoquinoline Adjuvants.
Fatty Acid-Mimetic Micelles for Dual Delivery of Antigens and Imidazoquinoline Adjuvants.
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DOI：
10.1021/acsbiomaterials.6b00408
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发表时间：
2017-02-13
影响因子：
5.8
通讯作者：
Wilson JT
中科院分区：
文献类型：
--
作者：
Sevimli S;Knight FC;Gilchuk P;Joyce S;Wilson JT
疫苗设计已经转向使用纯化的蛋白质亚单位疫苗，其提供增加的安全性和对抗原特异性的更大控制，但以免疫原性为代价。在这里，我们报告了一种新的基于聚合物的疫苗递送平台的开发，该平台通过蛋白抗原和Toll样受体7（TLR 7）激动剂咪喹莫特（IMQ）的共同递送来增强免疫力。由于IMQ在脂肪酸中的优先溶解性，通过可逆加成-断裂链转移（RAFT）聚合，合成了一系列嵌段共聚物胶束，其具有由甲基丙烯酸月桂酯（LMA）和甲基丙烯酸（MAA）组成的脂肪酸模拟核，以及由甲基丙烯酸吡啶二硫乙酯（PDSM）修饰的用于抗原缀合的聚乙二醇甲基醚甲基丙烯酸酯（PEGMA）冠。载体组成的50摩尔%的LMA（LMA 50）表现出最高的IMQ负载（2.2 w/w%），并显着增强免疫刺激能力的IMQ诱导树突状细胞成熟和促炎细胞因子的生产。模型抗原，卵清蛋白（OVA），结合到顶Q负载的LMA 50胶束的冠增强体外抗原摄取和交叉呈递的MHC I类（MHC-I）。与抗原和佐剂的可溶性制剂相比，用与IMQ和OVA共负载的载体对小鼠进行单次鼻内（IN）免疫引起显著更高的肺和全身CD 8 + T细胞应答和增加的血清IgG滴度。总的来说，这些数据表明，合理设计的脂肪酸模拟胶束增强细胞内抗原和IMQ的传递，并有潜力作为合成载体，用于增强亚单位疫苗的免疫原性。
Vaccine design has undergone a shift towards the use of purified protein subunit vaccines, which offer increased safety and greater control over antigen specificity, but at the expense of immunogenicity. Here we report the development of a new polymer-based vaccine delivery platform engineered to enhance immunity through the co-delivery of protein antigens and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ). Owing to the preferential solubility of IMQ in fatty acids, a series of block copolymer micelles with a fatty acid-mimetic core comprising lauryl methacrylate (LMA) and methacrylic acid (MAA), and a poly(ethylene glycol) methyl ether methacrylate (PEGMA) corona decorated with pyridyl disulfide ethyl methacrylate (PDSM) moieties for antigen conjugation were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Carriers composed of 50 mole% LMA (LMA50) demonstrated the highest IMQ loading (2.2 w/w%) and significantly enhanced the immunostimulatory capacity of IMQ to induce dendritic cell maturation and proinflammatory cytokine production. Conjugation of a model antigen, ovalbumin (OVA), to the corona of IMQ-loaded LMA50 micelles enhanced in vitro antigen uptake and cross-presentation on MHC class I (MHC-I). A single intranasal (IN) immunization of mice with carriers co-loaded with IMQ and OVA elicited significantly higher pulmonary and systemic CD8+ T cell responses and increased serum IgG titer relative to a soluble formulation of antigen and adjuvant. Collectively, these data demonstrate that rationally designed fatty acid-mimetic micelles enhance intracellular antigen and IMQ delivery and have potential as synthetic vectors for enhancing the immunogenicity of subunit vaccines.
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影响因子：
30.5
作者：
Chiu C;Openshaw PJ
通讯作者：
Openshaw PJ
DOI：
10.1073/pnas.1006044107
发表时间：
2010-09-21
影响因子：
11.1
作者：
Gao, Weiping;Liu, Wenge;Chilkoti, Ashutosh
通讯作者：
Chilkoti, Ashutosh
影响因子：
4.7
作者：
Foster, Suzanne;Duvall, Craig L.;Crownover, Emily F.;Hoffman, Allan S.;Stayton, Patrick S.
通讯作者：
Stayton, Patrick S.
影响因子：
11.5
作者：
Dudek, Arkadiusz Z.;Yunis, Caria;Miller, Jeffrey S.
通讯作者：
Miller, Jeffrey S.
影响因子：
4.1
作者：
FOTHERGI.LA;FOTHERGI.JE
通讯作者：
FOTHERGI.JE