Stabilization of HSV-2 Viral Vaccine Candidate by Spray Drying

Abstract

This work demonstrates that an HSV-2 candidate vaccine can be thermostabilized by spray drying to reduce cold chain demands. This work is also to optimize the process responses by varying spray dry parameters for pre-screened suitable excipients; and to determine the validity of current prescreening techniques. Vaccine activity losses were measured by in vitro plaque forming assay with Vero cell line. An accelerated storage condition of 45°C for 10 days was used to determine spray dried sample stability. Prescreening studies demonstrated that trehalose and sucrose were superior to other tested excipients spray dry thermal stabilization of HSV-2. Subsequent optimization by design of experiments (DOE) of activity responses to spray dry parameter changes demonstrated significant differences between trehalose and sucrose for stability of the viral vaccine. Model parameters included the drying conditions inlet temperature, spray gas flow rate, and solids concentration for the model responses of vaccine stabilization. Trehalose was an effective and robust stabilizing excipient for spray drying HSV-2 vaccine. In contrast, stabilization by sucrose was greatly dependent on the spray dry process parameters. These DOE differences indicated inadequate excipient selection by prescreening methods and the variability demonstrated current prescreening techniques may not be adequate for determining optimal excipients.