1. Biophysical characterization of polydisperse liposomal adjuvant formulations.
- Author
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Singh P, Matyas GR, Anderson A, and Beck Z
- Subjects
- Cholesterol chemistry, Cryoelectron Microscopy, Freeze Drying, Lipid A chemistry, Liposomes ultrastructure, Particle Size, Adjuvants, Immunologic chemistry, Lipid A analogs & derivatives, Liposomes chemistry, Saponins chemistry
- Abstract
Army Liposome Formulations (ALF) are potent adjuvants, of which there are two primary forms, lyophilized ALF (ALFlyo) containing monophosphoryl lipid A (MPLA) and ALF containing MPLA and QS21 (ALFQ). ALFlyo and ALFQ adjuvants are essential constituents of candidate vaccines for bacterial, viral, and parasitic diseases. They have been widely used in preclinical immunogenicity studies in small animals and non-human primates and are progressing to phase I/IIa clinical trials. ALFQ was prepared by adding saponin QS21 to small unilamellar liposome vesicles (SUVs) of ALF55 that contain 55 mol% cholesterol, whereas ALFlyo was created by reconstituting lyophilized SUVs of ALF43, consisting of 43 mol% cholesterol, in aqueous buffer solution. These formulations display heterogenous particle size distribution. Since biophysical characteristics of liposomes may impact their adjuvant potential, we characterized the particle size distribution and lamellarity of the individual liposome particles in ALFlyo and ALFQ formulations using cryo-electron microscopy and a newly developed MANTA technology. ALFlyo and ALFQ exhibited similar particle size distributions with liposomes ranging from 50 nm to several μm. However, fundamental differences were observed in the lamellar structures of the liposomes. ALFlyo displayed a greater number of multilamellar and multivesicular liposome particles, as compared to that in ALFQ, which was predominately unilamellar., Competing Interests: Declaration of competing interest ZB ang GRM are inventors of the following patents. The other authors declare no financial/personal interests. Alving and Beck, 167 Alving C.R. and Beck Z., Non-toxic Adjuvant Formulation Comprising a Monophosphoryl Lipid A (MPLA)-Containing Liposome Composition and a Saponin. Compositions and Methods for Vaccine Delivery, U.S. Patent No. 10,434,167, issued: October 8, 2019. Dutta et al., November 01 Dutta S., Matyas G.R., Alving C.R., Beck Z., Compositions and methods for vaccine delivery: Combination of a soluble, nearly full-length circumsporozoite protein of Plasmodium falciparum produced in E. coli with Army Liposomal Adjuvant containing QS-21 (ALFQ). Publication of WO2018201022A1, November 01, 2018., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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