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.
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