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Advanced manufacturing of microdisk vaccines for uniform control of material properties and immune cell function
Biomaterials Science ( IF 6.6 ) Pub Date : 2017-11-13 00:00:00 , DOI: 10.1039/c7bm00520b
Qin Zeng 1, 2, 3, 4 , Peipei Zhang 1, 2, 3, 4 , Xiangbin Zeng 1, 2, 3, 4 , Lisa H. Tostanoski 1, 2, 3, 4 , Christopher M. Jewell 1, 2, 3, 4, 5
Affiliation  

The continued challenges facing vaccines in infectious disease and cancer highlight a need for better control over the features of vaccines and the responses they generate. Biomaterials offer unique advantages to achieve this goal through features such as controlled release and co-delivery of antigens and adjuvants. However, many synthesis strategies lead to particles with heterogeneity in diameter, shape, loading level, or other properties. In contrast, advanced manufacturing techniques allow precision control of material properties at the micro- and nano-scale. These capabilities in vaccines and immunotherapies could allow more rational design to speed efficient design and clinical translation. Here we employed soft lithography to generate polymer microdisk vaccines with uniform structures and tunable compositions of vaccine antigens and toll like receptor agonists (TLRas) that serve as molecular adjuvants. Compared to conventional PLGA particles formed by emulsion, microdisks provided a dramatic improvement in the consistency of properties such as diameter. During culture with primary dendritic cells (DCs) from mice, microdisks were internalized by the cells without toxicity, while promoting co-delivery of antigen and TLRa to the same cell. Analysis of DC surface activation markers by flow cytometry revealed microdisk vaccines activated dendritic cells in a manner that depended on the level of TLRa, while antigen processing and presentation depended on the amount of antigen in the microdisks. Together, this work demonstrates the use of advanced manufacturing techniques to produce uniform vaccines that direct DC function depending on the composition in the disks.

中文翻译:

先进制造的微型磁盘疫苗,可统一控制材料特性和免疫细胞功能

疫苗在传染性疾病和癌症中所面临的持续挑战突出表明,需要更好地控制疫苗的特性及其产生的反应。生物材料通过诸如抗原和佐剂的控释和共递送等功能提供了实现此目标的独特优势。但是,许多合成策略导致粒子的直径,形状,负载水平或其他属性具有异质性。相反,先进的制造技术可以在微米和纳米级别上精确控制材料性能。疫苗和免疫疗法中的这些功能可以允许进行更合理的设计,以加快有效的设计和临床翻译的速度。在这里,我们采用软光刻技术来生成聚合物微盘疫苗,该疫苗具有统一的结构以及疫苗抗原和用作分子佐剂的Toll样受体激动剂(TLRas)的可调组成。与通过乳液形成的常规PLGA颗粒相比,微盘在性能(如直径)的一致性方面提供了显着改善。在与小鼠原代树突状细胞(DC)进行培养的过程中,微盘被细胞内化而没有毒性,同时促进了抗原和TLRa共同递送至同一细胞。通过流式细胞术对DC表面活化标记物的分析显示,微盘疫苗以依赖于TLRa水平的方式活化树突状细胞,而抗原的加工和呈递则取决于微盘中抗原的量。一起,
更新日期:2017-11-13
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