There is a currently a need to develop adjuvants that are best suited to simultaneously enhance immune responses, induce immunologic memory, improve patient compliance (i.e., reduce doses and inflammation), and provide vaccine shelf stability for stockpiling and global deployment to challenging environments. Biodegradable polyanhydrides have been investigated extensively to overcome such challenges. It has been shown that controlling copolymer composition can result in chemistry-dependent immunomodulatory capabilities. These studies have revealed that copolymers rich in sebacic acid (SA) are highly internalized by antigen presenting cells and confer improved shelf stability of encapsulated proteins, while copolymers rich in 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) also exhibit enhanced internalization by and activation of antigen presenting cells (APCs), in addition to providing superior retention of protein stability following encapsulation and release. However, to date, CPTEG:SA copolymers have not been synthesized and described. In this work, we hypothesized that new copolymers composed of CPTEG and SA would combine the advantages of both monomers in terms of enhanced thermal properties, maintaining antigenicity of encapsulated proteins following nanoparticle synthesis, and superior cellular internalization and activation by APCs, demonstrated by the upregulation of costimulatory markers CD80, CD86, and CD40, as well as the secretion of proinflammatory cytokines IL-6, IL-1β, and TNF-α. Herein, we describe the synthesis and design of novel CPTEG:SA nanoparticles with improved thermal properties, payload stability, and internalization by antigen presenting cells for applications in vaccine delivery. The performance of these new CPTEG:SA formulations was compared to that of traditional polyanhydride copolymers.

中文翻译：

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快速降解聚酸酐作为疫苗佐剂的合成与表征

当前需要开发最适合同时增强免疫反应，诱导免疫记忆，改善患者依从性（即减少剂量和炎症）并提供疫苗贮存稳定性的佐剂，以用于储存和全球部署到具有挑战性的环境。为了克服这些挑战，已经对可生物降解的聚酸酐进行了广泛的研究。已经显示，控制共聚物的组成可以导致化学依赖性的免疫调节能力。这些研究表明，富含癸二酸（SA）的共聚物被抗原呈递细胞高度内在化，并改善了被包封蛋白质的货架稳定性，而富含1,8-bis（p（羧基羧氧基）-3,6-二氧八辛烷（CPTEG）除在封装和释放后提供出色的蛋白质稳定性保持能力外，还通过抗原呈递细胞（APC）表现出增强的内在化和活化。但是，迄今为止，尚未合成和描述CPTEG：SA共聚物。在这项工作中，我们假设由CPTEG和SA组成的新型共聚物将结合两种单体的优势，包括增强的热性能，纳米合成后保持被包封蛋白质的抗原性，以及上调对APC的优异细胞内在化和活化作用。共刺激标记CD80，CD86和CD40以及促炎细胞因子IL-6，IL-1β和TNF-α的分泌。在这里，我们描述了新型CPTEG的合成和设计：具有改善的热性能，有效负载稳定性和抗原呈递细胞内在化作用的SA纳米颗粒，可用于疫苗输送。将这些新的CPTEG：SA配方的性能与传统的聚酸酐共聚物进行了比较。