Effect of leucine as an aerosolization enhancer on the bioactivity of spray dried viral-vectored vaccines for inhalation

Abstract

Aerosolization enhancers, like L-leucine, can improve deep-lung deposition of inhalable dry powders although the implications of their use have not yet been evaluated for sensitive biologics like viral vectored vaccines. This study investigates the effect of L-leucine concentrations (0–50 wt%) as an added component to the viral-encapsulating matrix comprised of mannitol and dextran, on aerosolization relative to bioactivity of spray dried human serotype 5 adenovirus. Modelling the intended purpose of inhalation, the aerodynamic properties (fine particle fraction and mass median aerodynamic diameter) of the powders were analyzed using a Next Generation Impactor. Overall, increasing the L-leucine concentration in the spray dried formulations improved the fine particle fraction (>40%) and reduced the aerodynamic diameter (<5 μm). However, bioactivity was negatively affected by the presence of L-leucine in the formulation and that demanded deeper investigation. The root cause for the declining bioactivity was finally attributed to aggregation of the adenovirus induced by L-leucine in the feed solution prior to spray drying, which was determined using a qViro-X particle counter. The intent of this study was to emphasize that advantages and disadvantages will exist with additives like an aerosolization enhancer, for this relatively new class of vaccines.