Fuerst Thomas R, Marin Alexander, Jeong Sarah, Kulakova Liudmila, Hlushko Raman, Gorga Katrina, Toth Eric A, Singh Nevil J, Andrianov Alexander K
Institute for Bioscience and Biotechnology Research, University of Maryland Rockville, Rockville, MD 20850, USA.
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
J Funct Biomater. 2025 Jan 19;16(1):34. doi: 10.3390/jfb16010034.
Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity-CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems.
丙型肝炎病毒（HCV）是一个重大的公共卫生问题，开发有效的HCV疫苗对于预防新感染至关重要。丙型肝炎病毒包膜E1E2异二聚体复合物和核心蛋白的超分子共组装及共呈递，为实现有效的体液免疫和细胞免疫提供了一种有吸引力的疫苗设计策略。出于这一目的，使用可生物降解的合成聚磷腈递送载体，将这两种抗原与一种免疫刺激剂（TLR 7/8激动剂）非共价组装成模拟病毒的聚合物纳米复合物（VMPN）。使用动态光散射和不对称流场-流分级方法对所得组装体进行表征，并通过低温电子显微镜直接观察其玻璃化状态下的情况。VMPN在体内相对于单个组分和铝佐剂疫苗的优势表现为更高的中和抗体滴度、促进平衡的IgG反应以及诱导针对核心蛋白的细胞免疫——CD4+ T细胞反应。由合成可生物降解载体实现的基于水性的抗原和免疫增强分子的自发共组装，为开发基于聚合物的超分子纳米疫苗系统提供了一条简单有效的途径。
