Thin-film freeze-drying of a bivalent Norovirus vaccine while maintaining the potency of both antigens

Abstract

A bivalent Norovirus vaccine candidate has been developed that contains Norovirus strain GI.1 Norwalk-virus like particles (VLP) and strain GII.4 Consensus VLP adsorbed on aluminum (oxy)hydroxide. The Norwalk and Consensus antigens have different stability profiles, making it challenging to prepare a dry powder form of the Norovirus vaccine while maintaining the potency of both antigens. In the present study, we tested the feasibility of converting the vaccine from a liquid suspension to dry powders by thin-film freeze-drying (TFFD). With the proper amount of trehalose and/or sucrose as cryoprotectant (i.e. sucrose alone at 4.55% or 5.55%, w/v, or trehalose at 3–4% with 0.55% of sucrose), TFFD can be applied to successfully convert the Norovirus vaccine candidate into dry powders without causing antigen loss or particle aggregation, while maintaining the relative potency of both antigens within a specified acceptable range. In an accelerated stability study, the potency of the antigens was also maintained in the specified acceptable range after the dry powders prepared by TFFD in the presence of 5.55% (w/v) of sucrose were stored for eight weeks at 40 °C, 75% relative humidity. It is concluded that it is feasible to apply TFFD to convert the Norovirus vaccine from a liquid suspension to stable dry powders.