New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, China.
Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, 100071, China.
J Nanobiotechnology. 2024 Aug 27;22(1):513. doi: 10.1186/s12951-024-02767-z.
The application of nanoscale scaffolds has become a promising strategy in vaccine design, with protein-based nanoparticles offering desirable avenues for the biocompatible and efficient delivery of antigens. Here, we presented a novel endogenous capsid-forming protein, activated-regulated cytoskeleton-associated protein (ARC), which could be engineered through the plug-and-play strategy (SpyCatcher3/SpyTag3) for multivalent display of antigens. Combined with the self-assembly capacity and flexible modularity of ARC, ARC-based vaccines elicited robust immune responses against Mpox or SARS-CoV-2, comparable to those induced by ferritin-based vaccines. Additionally, ARC-based nanoparticles functioned as immunostimulants, efficiently stimulating dendritic cells and facilitating germinal center responses. Even without adjuvants, ARC-based vaccines generated protective immune responses in a lethal challenge model. Hence, this study showed the feasibility of ARC as a novel protein-based nanocarrier for multivalent surface display of pathogenic antigens and demonstrated the potential of exploiting recombinant mammalian retrovirus-like protein as a delivery vehicle for bioactive molecules.
纳米支架的应用已成为疫苗设计中一种很有前途的策略，基于蛋白质的纳米颗粒为生物相容性和高效递呈抗原提供了理想的途径。在这里，我们提出了一种新型的内源性衣壳形成蛋白，即激活调节细胞骨架相关蛋白（ARC），它可以通过插件和播放策略（SpyCatcher3/SpyTag3）进行工程化，用于多价展示抗原。结合 ARC 的自组装能力和灵活的模块化，基于 ARC 的疫苗可引发针对 Mpox 或 SARS-CoV-2 的强大免疫反应，与基于铁蛋白的疫苗相当。此外，基于 ARC 的纳米颗粒作为免疫刺激剂，可有效刺激树突状细胞并促进生发中心反应。即使没有佐剂，基于 ARC 的疫苗也能在致死性挑战模型中产生保护性免疫反应。因此，本研究表明了 ARC 作为一种新型的基于蛋白质的纳米载体用于多价表面展示病原体抗原的可行性，并展示了利用重组哺乳动物逆转录病毒样蛋白作为生物活性分子传递载体的潜力。
