Du Fanfan, Yuk Simseok A, Qian Yuan, Vincent Michael P, Bobbala Sharan, Abbott Tirzah M, Kim Hyeohn, Li Yang, Li Haoyu, Yi Sijia, Qiao Baofu, Scott Evan A
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
Northwestern University Atomic and Nanoscale Characterization Experimental Center, Evanston, IL 60208, USA.
Res Sq. 2024 Apr 25:rs.3.rs-4177821. doi: 10.21203/rs.3.rs-4177821/v1.
The development of subunit vaccines that mimic the molecular complexity of attenuated vaccines has been limited by the difficulty of intracellular co-delivery of multiple chemically diverse payloads at controllable concentrations. We report on hierarchical hydrogel depots employing simple poly(propylene sulfone) homopolymers to enable ratiometric loading of a protein antigen and four physicochemically distinct adjuvants in a hierarchical manner. The optimized vaccine consisted of immunostimulants either adsorbed to or encapsulated within nanogels, which were capable of noncovalent anchoring to subcutaneous tissues. These 5-component nanogel vaccines demonstrated enhanced humoral and cell-mediated immune responses compared to formulations with standard single adjuvant and antigen pairing. The use of a single simple homopolymer capable of rapid and stable loading and intracellular delivery of diverse molecular cargoes holds promise for facile development and optimization of scalable subunit vaccines and complex therapeutic formulations for a wide range of biomedical applications.
模仿减毒疫苗分子复杂性的亚单位疫苗的开发受到限制，原因在于难以在可控浓度下将多种化学性质不同的有效载荷进行细胞内共递送。我们报道了一种分层水凝胶储库，它采用简单的聚（丙砜）均聚物，能够以分层方式对一种蛋白质抗原和四种物理化学性质不同的佐剂进行比例加载。优化后的疫苗由吸附在纳米凝胶上或包裹在纳米凝胶内的免疫刺激剂组成，这些纳米凝胶能够非共价锚定到皮下组织。与标准单一佐剂和抗原配对的制剂相比，这些五组分纳米凝胶疫苗表现出更强的体液免疫和细胞介导免疫反应。使用一种能够快速、稳定地加载并在细胞内递送多种分子货物的单一简单均聚物，有望为广泛的生物医学应用轻松开发和优化可扩展的亚单位疫苗及复杂治疗制剂。
