Thermostabilization of a model viral-vectored oral thin film vaccine

Abstract

Vaccines rely on a global cold chain to maintain vaccine potency throughout the product life cycle. Existing vaccine thermostabilization methods like lyophilization and spray-drying impart significant stress on the vaccine, reducing its potency. Therefore, dissolvable oral thin films (OTFs) have emerged as an alternative thermostabilizing vaccine delivery platform wherein the vaccine is immobilized in a polymer-sugar matrix and administered to the oral mucosa.

Herein, we demonstrate the feasibility of incorporating a model adenovirus vector into an OTF (Ad5 OTF) using a simple one-hour solvent casting process, and we demonstrate retention of the adenovirus infectious titer during storage, as assessed by flow cytometric titering. Increasing Tris buffer concentration and changing the surfactant from a nonionic Tween 80 to a zwitterionic poly(maleic anhydride-alt-1-octadecene) substituted with 3-(dimethylamino)propylamine (PMAL) and increasing its concentration improved the six-day ambient temperature stability by nearly 4-fold.

A 2³ full factorial design of experiment investigating the influence of trehalose, PEG, and PMAL concentration demonstrated that PMAL and trehalose concentration have the greatest impact on stability of Ad5 OTFs, improving the six-day ambient temperature stability by 250-fold, compared to the first formulation evaluated herein. The thermal stabilization of Ad5 OTFs prepared with a simple one-hour casting process demonstrates the scale-up and scale-out potential for this OTF formulation as a vaccine delivery platform, improving the accessibility of vaccines.

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Materials

Pullulan and trehalose were purchased from Hayashibara (Okayama, Japan). Dimethyl sulfone, Trizma base, and Tween 80 were purchased from Sigma-Aldrich (Oakville, Canada). Glycerol was purchased from Caledon Laboratory Chemicals (Georgetown, Canada). Poly(Ethylene) Glycol 8000 Da (PEG), 0.5 % trypsin-EDTA, heat inactivated fetal bovine serum, penicillin/streptomycin, and minimum essential medium with Earle’s salts (MEM) were purchased from ThermoFisher Scientific (Waltham, United States). Poly(maleic anhydride-alt-1-octadecene) substituted with 3-(dimethylamino)propylamine (PMAL) was purchased from Anatrace (Maumee, United States).

Annika Yardy, Iris Q. Wang, Yva Rasco, Grace Lenihan, James D. Mayo, Jingyu Mu, Benjamin Macphail, Mark Larché, Alex Adronov, Thermostabilization of a model viral-vectored oral thin film vaccine, International Journal of Pharmaceutics, 2025, 125662, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125662.