Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
Biomaterials. 2011 Oct;32(28):6815-22. doi: 10.1016/j.biomaterials.2011.05.063. Epub 2011 Jun 24.
Techniques in materials design, immunophenotyping, and informatics can be valuable tools for using a molecular based approach to design vaccine adjuvants capable of inducing protective immunity that mimics a natural infection but without the toxic side effects. This work describes the molecular design of amphiphilic polyanhydride nanoparticles that activate antigen presenting cells in a pathogen-mimicking manner. Biodegradable polyanhydrides are well suited as vaccine delivery vehicles due to their adjuvant-like ability to: 1) enhance the immune response, 2) preserve protein structure, and 3) control protein release. The results of these studies indicate that amphiphilic nanoparticles possess pathogen-mimicking properties as evidenced by their ability to activate dendritic cells similarly to LPS. Specific molecular descriptors responsible for this behavior were identified using informatics analyses, including the number of backbone oxygen moieties, percent of hydroxyl end groups, polymer hydrophobicity, and number of alkyl ethers. Additional findings from this work suggest that the molecular characteristics mediating APC activation are not limited to hydrophobicity but vary in complexity (e.g., presentation of oxygen-rich molecular patterns to cells) and elicit unique patterns of cellular activation. The approach outlined herein demonstrates the ability to rationally design pathogen-mimicking nanoparticle adjuvants for use in next-generation vaccines against emerging and re-emerging diseases.
在材料设计、免疫表型分析和信息学方面的技术可以成为使用基于分子的方法设计疫苗佐剂的有价值的工具，这些佐剂能够诱导模仿自然感染但没有毒副作用的保护性免疫。这项工作描述了两亲性聚酸酐纳米粒子的分子设计，这些纳米粒子以类似病原体的方式激活抗原呈递细胞。可生物降解的聚酸酐由于具有佐剂样特性而非常适合作为疫苗递送载体：1）增强免疫反应，2）保持蛋白质结构，3）控制蛋白质释放。这些研究的结果表明，两亲性纳米粒子具有类似病原体的特性，这可以证明它们能够像 LPS 一样激活树突状细胞。使用信息学分析确定了负责这种行为的特定分子描述符，包括主链氧部分的数量、羟基端基的百分比、聚合物疏水性和烷基醚的数量。这项工作的其他发现表明，介导 APC 激活的分子特征不仅限于疏水性，而且复杂程度不同（例如，向细胞呈现富含氧的分子模式），并引发独特的细胞激活模式。本文概述的方法证明了能够合理设计用于针对新兴和重现疾病的下一代疫苗的类似病原体的纳米粒子佐剂的能力。
