Development of (Inhalable) Dry Powder Formulations of AS01B-Containing Vaccines Using Thin-Film Freeze-Drying.

ABSTRACT

AS01B is a liposomal formulation of two immunostimulants namely 3-O-desacyl-4́-monophosphoryl lipid A (MPL) and QS-21. The liposomal formulation of AS01B reduces the endotoxicity of MPL and the lytic activity of QS-21. The AS01B-adjuvanted Shingrix vaccine is marketed in a two-vial presentation, with the liquid AS01B liposomes in one vial and the antigen as a dry powder in another vial. In the present study, we tested the feasibility of applying thin-film freeze-drying (TFFD) to engineer dry powders of the AS01B liposomal adjuvant alone or vaccines containing AS01B as an adjuvant. Initially, we showed that after the AS01B liposomal adjuvant was subjected to TFFD using sucrose as a stabilizer at 4% w/v, the particle size distribution of AS01B 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 AS01B (AS01B/OVA) that subjecting the AS01B/OVA vaccine to TFFD and subsequent reconstitution did not negatively affect the AS01B liposome particle size, nor the immunogenicity of the vaccine. Importantly, the thin-film freeze-dried AS01B/OVA vaccine, unlike its liquid counterpart, was not sensitive to repeated freezing-and-thawing. The developed AS01B/OVA dry powder also showed the desirable aerosol properties (i.e., fine particle fraction of 66.3 ± 4.9% and mass median aerodynamic diameter of 2.4 ± 0.1 µm) for potential pulmonary administration. Finally, the feasibility of using TFFD to prepare dry powders of AS01B-adjuvanted vaccines was further confirmed using AS01B-adjuvanted Fluzone Quadrivalent and Shingrix, which contains AS01B. It is concluded that the TFFD technology can enable the formulation of AS01B-adjuvanted vaccines as freezing-insensitive, inhalable dry powders in a single-vial presentation.