多酚-生物大分子纳米载体的可控组装及其在疫苗传输中的应用

The addition of adjuvant is typically required to elicit protective immunity. However, the mostly used adjuvants such as aluminum salts usually result in weak cellular immune response and could cause severe side effects. Engineering of vaccine nanocarriers using nanoparticles has attracted great interests since nanoparticles can act as an adjuvant or simultaneously deliver antigens to improve immune responses. Polyphenols are biocompatible and have multiple non-covalent interactions with biomacromolecules (e.g., antigen), which make them as a good candidate for the assembly of vaccine nanocarriers. Herein, vaccine nanocarriers are fabricated by polyphenols and antigens, followed by functionalization of the nanocarriers with adjuvants and targeting molecules, to improve antigen delivery efficacy and specific immune responses. The influence of the assembly process and polyphenol types on the physiological properties of the nanocarriers will be investigated. The mechanism of immunological enhancement will be explored. This project will provide a new avenue for the design and development of polyphenol-based vaccine nanocarriers for improved vaccine delivery and vaccine immunogenicity.

添加佐剂是增强疫苗免疫原性的重要手段，但铝盐等常用佐剂在提升细胞免疫应答方面较差，并引起诸多不良反应。纳米粒子在传输抗原的同时也可以传输或充当疫苗佐剂进而提高免疫原性，因此利用纳米粒子作为疫苗载体是新型疫苗佐剂的研究热点。多酚具有良好的生物安全性，并且能够与生物大分子（例如抗原）发生多种非共价键相互作用，这使其在构筑疫苗载体中具有重要应用价值。本项目拟利用多酚和抗原制备纳米疫苗载体，并引入具有佐剂活性和特异靶向性能的分子，实现抗原的靶向性传输和特异性免疫应答。在此基础上，探索多酚形成纳米疫苗载体的可控组装规律和影响因素，实现多酚纳米疫苗载体的可控组装。同时结合细胞和动物实验，探究多酚纳米疫苗载体提高疫苗免疫原性的作用机制。该研究为多酚用于纳米疫苗载体组装以及提高疫苗免疫原性和传输效率提供理论依据。

纳米粒子在传输抗原的同时也可以传输或充当疫苗佐剂进而提高免疫原性，因此利用纳米粒子递送疫苗是一个研究热点。多酚具有良好的生物安全性，并且能够与生物大分子（例如抗原）发生多种非共价键相互作用，这使其在构筑疫苗载体中具有重要应用价值。本项目基于金属-多酚网络（Metal-Phenolic Networks，MPN）涂层和多酚蛋白相互作用构筑了两种纳米疫苗，不但能够激活抗原递呈细胞诱导肿瘤特异性免疫应答，抑制肿瘤生长，而且具有良好的生物相容性，本工作为多酚用于纳米疫苗载体组装以及提高疫苗免疫原性和传输效率提供理论依据，为进一步优化纳米疫苗递送系统奠定了基础。