Chief, Laboratory of Adjuvant & Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.
Laboratory of Adjuvant & Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.
Curr Top Microbiol Immunol. 2021;433:1-28. doi: 10.1007/82_2020_227.
Development of liposome-based formulations as vaccine adjuvants has been intimately associated with, and dependent on, and informed by, a fundamental understanding of biochemical and biophysical properties of liposomes themselves. The Walter Reed Army Institute of Research (WRAIR) has a fifty-year history of experience of basic research on liposomes; and development of liposomes as drug carriers; and development of liposomes as adjuvant formulations for vaccines. Uptake of liposomes by phagocytic cells in vitro has served as an excellent model for studying the intracellular trafficking patterns of liposomal antigen. Differential fluorescent labeling of proteins and liposomal lipids, together with the use of inhibitors, has enabled the visualization of physical locations of antigens, peptides, and lipids to elucidate mechanisms underlying the MHC class I and class II pathways in phagocytic APCs. Army Liposome Formulation (ALF) family of vaccine adjuvants, which have been developed and improved since 1986, and which range from nanosize to microsize, are currently being employed in phase 1 studies with different types of candidate vaccines.
脂质体作为疫苗佐剂的制剂的发展与脂质体本身的生化和物理特性的基本理解密切相关，并依赖于这一理解，同时也为这一理解提供了信息。沃尔特·里德陆军研究所（WRAIR）在脂质体的基础研究、脂质体作为药物载体的开发以及脂质体作为疫苗佐剂制剂的开发方面有着 50 年的经验。体外吞噬细胞对脂质体的摄取一直是研究脂质体抗原细胞内运输模式的极好模型。蛋白质和脂质体脂质的差异荧光标记，以及抑制剂的使用，使抗原、肽和脂质的物理位置可视化，从而阐明吞噬性 APC 中 MHC Ⅰ类和Ⅱ类途径的机制。自 1986 年以来开发和改进的 Army Liposome Formulation（ALF）疫苗佐剂家族，从纳米级到微米级不等，目前正在不同类型候选疫苗的 1 期研究中使用。
