Wang Xiang, Xia Haiyang, Li Tiantian, Zuo Qinhua, Wang Zhen, Yan Kangjian, Xu Zejun, Xue Wei, Sun Guodong, Liu Zonghua, Zhang Yi
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Engineering Technology Research Center of Drug Carrier of Guangdong, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.
College of Pharmacy, Jinan University, Guangzhou, 510630, China.
Adv Healthc Mater. 2025 Jan;14(1):e2401625. doi: 10.1002/adhm.202401625. Epub 2024 Nov 3.
The development of cancer vaccines is at the forefront of cancer immunotherapy. Most existing strategies to induce an efficient anti-tumor immune response rely on molecular adjuvants and the incorporation of complex synthetic vectors into vaccine formulations. In contrast, this study introduces a one-step engineering technique to assemble the model antigen, Ovalbumin (OVA), into amyloid aggregates, leveraging biomimetic folding and aggregation to create non-fibrillar OVA globular aggregates and OVA amyloid-like fibrils as single-component, adjuvant-free vaccines. Notably, the OVA amyloid-like fibrils induced stronger immune responses compared to the native form, as evidenced by robust humoral immune reactions and the establishment of immune memory. These enhanced responses can be attributed to the self-adjuvant effect of the unique assembled structure, which preserves antigenic epitopes, improves antigen stability, facilitates antigen internalization, prolongs retention at the injection site, enhances antigen trafficking to the lymphoid organs, and promotes increased secretion of antibodies and cytokines. Furthermore, the efficacy of the vaccine was validated in a high OVA-expressing tumor model, demonstrating the potential of OVA amyloid-like fibrils as an effective vaccine for cancer immunoprevention. This minimalist self-adjuvant vaccine strategy holds promising implications for cancer immunotherapy and can inform the design of other protein antigen-based vaccines.
癌症疫苗的研发处于癌症免疫治疗的前沿。目前大多数诱导有效抗肿瘤免疫反应的策略依赖于分子佐剂以及将复杂的合成载体纳入疫苗配方。相比之下，本研究引入了一种一步工程技术，将模型抗原卵清蛋白（OVA）组装成淀粉样聚集体，利用仿生折叠和聚集来创建非纤维状OVA球状聚集体和OVA淀粉样纤维，作为单组分、无佐剂的疫苗。值得注意的是，与天然形式相比，OVA淀粉样纤维诱导了更强的免疫反应，强大的体液免疫反应和免疫记忆的建立证明了这一点。这些增强的反应可归因于独特组装结构的自佐剂效应，该效应保留了抗原表位，提高了抗原稳定性，促进了抗原内化，延长了在注射部位的停留时间，增强了抗原向淋巴器官的转运，并促进了抗体和细胞因子分泌的增加。此外，该疫苗在高表达OVA的肿瘤模型中得到了验证，证明了OVA淀粉样纤维作为癌症免疫预防有效疫苗的潜力。这种极简主义的自佐剂疫苗策略对癌症免疫治疗具有广阔的前景，并可为其他基于蛋白质抗原的疫苗设计提供参考。
