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

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.

Highlights

• Dry powder formulations of AS01B-adjuvanted vaccines were developed using TFFD.

• The Liposome integrity and antigen immunogenicity were preserved.

• The dry powders have good aerosol performance for potential pulmonary administration.

• The dry powders are freezing-insensitive.

• The dry powders enable single-vial presentation of AS01B-adjuvanted vaccines.

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.

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Khaled AboulFotouh, Haiyue Xu, Chaeho Moon, Robert O. Williams, Zhengrong Cui,
Development of (Inhalable) Dry Powder Formulations of AS01B-Containing Vaccines Using Thin-Film Freeze-Drying,
International Journal of Pharmaceutics,
Volume 622, 2022, 121825, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2022.121825.