College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
Jinhua Institute of Zhejiang University, 403 Yongkang Street, Jinhua 321299, China.
Mol Pharm. 2023 Nov 6;20(11):5668-5681. doi: 10.1021/acs.molpharmaceut.3c00536. Epub 2023 Oct 19.
Despite significant progress in vaccine development, especially in the fight against viral infections, many unexplored areas remain including innovative adjuvants, diversification of vaccine formulations, and research into the coordination of humoral and cellular immune mechanisms induced by vaccines. Effective coordination of humoral and cellular immunity is crucial in vaccine design. In this study, we used the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or ovalbumin (OVA) as antigen models and CpG DNA (an activator of toll-like receptor 9, TLR9) as an adjuvant to prepare a multitargeted liposome (LIPO) vaccine. Once equipped with the ability to target lymph nodes (LN) and the endoplasmic reticulum (ER), the LIPO vaccine significantly enhances the cross-presentation ability of antigen-presenting cells (APCs) for exogenous antigens through the ER-associated protein degradation (ERSD) mechanism. Additionally, the vaccine could fine-tune the efficiency of ER-targeted antigen delivery, actively regulating the presentation of exogenous antigen proteins via the major histocompatibility complex (MHC-I) or MHC-II pathways. Immune data from in vivo mouse experiments indicated that the LIPO vaccine effectively stimulated both humoral and cellular immune responses. Furthermore, it triggers immune protection by establishing a robust and persistent germinal center. Moreover, the multifunctionality of this LIPO vaccine extends to the fields of cancer, viruses, and bacteria, providing insights for skilled vaccine design and improvement.
尽管在疫苗开发方面取得了重大进展，特别是在对抗病毒感染方面，但仍有许多未探索的领域，包括创新佐剂、疫苗制剂的多样化以及研究疫苗诱导的体液和细胞免疫机制的协调。有效的体液和细胞免疫协调是疫苗设计的关键。在这项研究中，我们使用严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的刺突蛋白（S）或卵清蛋白（OVA）作为抗原模型，并用 CpG DNA（一种 Toll 样受体 9，TLR9 的激活剂）作为佐剂来制备多靶向脂质体（LIPO）疫苗。一旦具有靶向淋巴结（LN）和内质网（ER）的能力，LIPO 疫苗通过 ER 相关蛋白降解（ERSD）机制显著增强了抗原呈递细胞（APC）对外源抗原的交叉呈递能力。此外，该疫苗可以微调 ER 靶向抗原递呈的效率，通过主要组织相容性复合体（MHC-I 或 MHC-II）途径主动调节外源抗原蛋白的呈递。体内小鼠实验的免疫数据表明，LIPO 疫苗有效地刺激了体液和细胞免疫反应。此外，它通过建立强大而持久的生发中心来触发免疫保护。此外，这种 LIPO 疫苗的多功能性还扩展到癌症、病毒和细菌领域，为熟练的疫苗设计和改进提供了见解。
