用于主动调节细胞和体液免疫的脂质体疫苗。
Liposome Vaccine for Active Regulation of Cellular and Humoral Immunity.
发表日期:2023 Oct 19
作者:
Lihua Luo, Zhenyu Luo, Litong Wang, Yilong Hu, Junlei Zhang, Hang Yin, Jian You
来源:
MOLECULAR PHARMACEUTICS
摘要:
尽管疫苗开发,特别是在对抗病毒感染方面取得了重大进展,但许多尚未探索的领域仍然存在,包括创新佐剂、疫苗配方的多样化以及疫苗诱导的体液和细胞免疫机制的协调研究。体液免疫和细胞免疫的有效协调对于疫苗设计至关重要。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,并使用CpG DNA(Toll样受体9的激活剂,TLR9)作为抗原模型。用于制备多靶点脂质体(LIPO)疫苗的佐剂。一旦具备靶向淋巴结(LN)和内质网(ER)的能力,LIPO疫苗可通过ER相关蛋白降解(ERSD)显着增强抗原呈递细胞(APC)对外源抗原的交叉呈递能力。 ) 机制。此外,该疫苗可以微调内质网靶向抗原递送的效率,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。小鼠体内实验的免疫数据表明,LIPO 疫苗有效刺激了体液和细胞免疫反应。此外,它还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疫苗的多功能性延伸到癌症、病毒和细菌领域,为熟练的疫苗设计和改进提供了见解。
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.