Development of Dry Powder Formulations of AS01Bcontaining vaccines using Thin-Film Freeze-Drying

AS01 B is a liposomal formulation of two immunostimulants namely 3-O-desacyl-4’-monophosphoryl lipid A (MPL) and QS-21. The liposomal formulation of AS01 B reduces the endotoxicity of MPL and the lytic activity of QS-21; however, it renders the adjuvant sensitive to accidental slow freezing. The liposomal formulation also represents a major challenge towards the formulation of dry powders of vaccines containing AS01 B . In the present study, we tested the feasibility of applying thin-film freeze-drying (TFFD) to engineer dry powders of the AS01 B liposomal adjuvant alone or vaccines containing AS01 B as an adjuvant. Initially, we showed that after the AS01 B liposomal adjuvant was subjected to TFFD using sucrose as a stabilizer at 4% w/v , the particle size distribution of AS01 B liposomes reconstituted from the dry powder was identical to the liquid adjuvant before drying. We then showed using ovalbumin (OVA) as a model antigen adjuvanted with AS01 B (AS01 B /OVA) that subjecting the AS01 B /OVA vaccine to TFFD and subsequent reconstitution did not negatively affect the AS01 B liposome integrity, nor the immunogenicity of the vaccine. Importantly, the thin-film freeze-dried vaccine was not sensitive to repeated freezing-and-thawing. Finally, the feasibility of using TFFD to prepare dry powders of AS01 B -adjuvanted vaccines was further confirmed using AS01 B -adjuvanted Fluzone Quadrivalent and Shingrix, which contains AS01 B . It is concluded that the TFFD technology can enable the formulation of AS01 B -adjuvanted vaccines as freezing-insensitive dry powders in single-vial presentation.