Comparative stability study of lyophilised aluminium hydroxide adjuvanted vaccine formulations containing a monoclonal antibody as a model antigen and methods used for their characterisation

This study evaluates the stability of lyophilised aluminium hydroxide adjuvanted vaccine formulations during stress testings at elevated temperatures. Trehalose, dextran, HES, PVP, saccharose and sorbitol were used as excipients to protect both vaccine components – protein/antigen and an adjuvant – during lyophilisation from freezing- and dehydration stresses. Exemplary vaccine components were abagovomab, a monoclonal anti idiotypic antibody developed as an immuno-vaccine for the treatment of ovarian cancer and aluminium hydroxide adjuvant. All six excipients protected the monoclonal antibody abagovomab from denaturation and loss in potency as detected with sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). Enzyme-linked immunosorbent assay (ELISA) could show maintenance of abagovomab potency within the lyophilised samples throughout the stress testings as could also be shown for stress tested drug substance. Particle size analysis, sedimentation assay and wide angle X-ray diffraction (WAXD) revealed that dextran, hydroxyethyl starch (HES) and polyvinyl pyrrolidone K 25 (PVP) particularly enhanced stability of the adjuvant within a vaccine formulation during stress testing. The present study could further demonstrate the applicability of Nile Red fluorescence microscopy and adsorption studies for in-depth characterisation of freeze dried vaccine formulations.