Similarities and differences of chemical compositions and physical and functional properties of adjuvant system 01 and army liposome formulation with QS21

Abstract

A vaccine adjuvant known as Adjuvant System 01 (AS01) consists of liposomes containing a mixture of natural congeners of monophosphoryl lipid A (MPL®) obtained from bacterial lipopolysaccharide, and a tree saponin known as QS21. Two vaccines containing AS01 as the adjuvant have been licensed, including a malaria vaccine (Mosquirix®) approved by World Health. Organization and European Medicines Agency for use in sub-Saharan Africa, and a shingles vaccine (Shingrix®) approved by the U.S. Food and Drug Administration. The success of the AS01 vaccine adjuvant has led to the development of another liposomal vaccine adjuvant, referred to as Army Liposome Formulation with QS21 (ALFQ). Like AS01, ALFQ consists of liposomes containing monophosphoryl lipid A (as a synthetic molecule known as 3D-PHAD®) and QS21 as adjuvant constituents, and the polar headgroups of the liposomes of AS01 and ALFQ are similar. We compare here AS01 with ALFQ with respect to their similar and different liposomal chemical structures and physical characteristics with a goal of projecting some of the likely mechanisms of safety, side effects, and mechanisms of adjuvanticity. We hypothesize that some of the side effects exhibited in humans after injection of liposome-based vaccines might be caused by free fatty acid and lysophospholipid released by enzymatic attack of liposomal phospholipid by phospholipase A2 at the injection site or systemically after injection.

Micro‐ and Nanomanufacturing for Biomedical Applications and Nanomedicine: A Perspective

“…Mean size: 100 nm [298] Liposome Solvent evaporationhomogenization (high-pressure microfluidization)…”

A Reliable Quantification of Cholesterol and 25-Hydroxycholesterol in Liposomal Adjuvant Formulation by Liquid Chromatography High-Resolution Tandem Mass Spectrometry

“…Liposomes have been used also as carriers for chemotherapy targeting agents and MRI contrast agents − and have been utilized as models for studying biomembranes . Recently, liposomes have been employed as vaccine adjuvants, for example, AS01 has been used in vaccines against malaria, shingles, and respiratory syncytial virus (RSV). − Army Liposome formulation with QS21 (ALFQ) , has been used in several phase I vaccine clinical trials targeting malaria antigens, Campylobacter diarrhea, SARS-Cov-2, and HIV . The efficacy of liposomes in various applications is influenced by their quality attributes such as size, polydispersity, lamellarity, bilayer fluidity, and encapsulation efficiency, which are controlled by the lipid and cholesterol ratios in the formulation.…”

“…In liposome formulations, cholesterol, as one of the major components, exerts a profound influence on the properties of the lipid bilayer. It plays a crucial role in the structural stability and modulation of membrane permeability and fluidity. , For these reasons, high percentages of cholesterol relative to total lipids are often incorporated in liposomal formulation . However, in aqueous solution during the manufacture and storage of liposomes, cholesterol undergoes oxidative degradation to generate oxidative products; for example, 25-hydroxycholesterol formed from autoxidation via hydroperoxide intermediates .…”

“…The presence of the hydroxyl group at C25, in addition to hydroxyl at C3 in 25-hydroxycholesterol alters the amphiphilic properties of the molecule causing membrane expansion leading to an increased membrane bilayer . Furthermore, cholesterol functions to abrogate the hemolytic property of QS21 in liposome formulations containing QS21, such as AS01, immune-stimulating complexes (ISCOMs) or Matrix-M, − and ALFQ, , which are currently employed as adjuvants in several vaccines. We have shown that detoxification of QS21 in ALFQ is dependent on the amount of cholesterol in the formulation .…”

“… 23 , 24 For these reasons, high percentages of cholesterol relative to total lipids are often incorporated in liposomal formulation. 16 However, in aqueous solution during the manufacture and storage of liposomes, cholesterol undergoes oxidative degradation to generate oxidative products; for example, 25-hydroxycholesterol formed from autoxidation via hydroperoxide intermediates. 25 The formation of an oxidative product such as 25-hydroxycholesterol has been observed to induce changes in the characteristics of plasma membranes.…”