Zhang Wen, Cui Haicheng, Xu Jixuan, Shi Mingze, Bian Lijun, Cui Lili, Jiang Chunlai, Zhang Yong
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
R&D Center, Changchun BCHT Biotechnology Co., Changchun 130012, China.
J Control Release. 2025 Feb 10;378:573-587. doi: 10.1016/j.jconrel.2024.12.044. Epub 2024 Dec 25.
Recently, adjuvants have received increasing attention as essential vaccine components. Nearly 100 years have passed since Gaston Roman introduced the concept of adjuvants in 1925, during which numerous preclinical and clinical studies related to vaccine adjuvants have been conducted. However, to date, only a few adjuvants have been successfully used in marketed vaccines. This low clinical translational efficiency is mainly owing to the lack of comprehensive and in-depth understanding of the mechanisms of action of adjuvants in complex biological systems. In fact, MF59 is the first non‑aluminum adjuvant applied in approved human vaccines and is still used today; however, many unknowns regarding its mechanism of action remain. Therefore, in this review, the current status of the mechanism of action of MF59 and MF59-like adjuvants is discussed based on evidence-based temporal and spatial processes of immune-regulatory events. Moreover, the key factors of MF59 and MF59-like adjuvants that regulate humoral and cellular immune responses have been summarized. In addition, studies on the distribution and elimination of both antigens and adjuvants were analyzed based on published studies to gain mechanistic insights into the safety of MF59-adjuvanted vaccines. This review will not only benefit future prospects for the development of novel squalene-based adjuvants and their use in clinical applications but will also be valuable for future mechanistic investigations on other vaccine adjuvants.
近年来，佐剂作为疫苗的重要组成部分受到了越来越多的关注。自1925年加斯顿·罗曼提出佐剂概念以来，已经过去了近100年，在此期间，开展了许多与疫苗佐剂相关的临床前和临床研究。然而，迄今为止，只有少数佐剂成功应用于上市疫苗。这种较低的临床转化效率主要是由于对佐剂在复杂生物系统中的作用机制缺乏全面深入的了解。事实上，MF59是第一种应用于获批人用疫苗的非铝佐剂，至今仍在使用；然而，其作用机制仍有许多未知之处。因此，在本综述中，基于免疫调节事件的循证时空过程，讨论了MF59和类MF59佐剂作用机制的现状。此外，总结了MF59和类MF59佐剂调节体液免疫和细胞免疫反应的关键因素。此外，基于已发表的研究分析了抗原和佐剂的分布与消除情况，以深入了解MF59佐剂疫苗的安全性机制。本综述不仅将有助于基于角鲨烯的新型佐剂的未来开发前景及其在临床应用中的使用，也将对未来其他疫苗佐剂的作用机制研究具有重要价值。
