Development of a thermal stabilizer formulation optimized by response surface methodology for Senecavirus A antigen.

Abstract

Numerous members of the family Picornaviridae, such as the Senecavirus A (SVA) and foot-and-mouth disease virus (FMDV), exhibit thermal instability, resulting in the dissociation of viral particles, which affects the insufficient potency of the vaccine. Based on this characteristic, this study aimed to maintain the thermal stability of SVA by supplementing it with a stabilizer. Excipients, such as sucrose, mannitol, sorbitol, polyethylene glycol (PEG), L-arginine (L-Arg), glutamic acid (Glu), polyvinyl pyrrolidone (PVP), bovine serum albumin (BSA), and potassium chloride (KCl) dissolved in Tris-HCl buffer solution, retained the infectivity of SVA in the thermostability assay. Thermal stability formulations were developed by combining different excipients in disaccharide polyol systems and optimizing formulations using the Box-Behnken experimental design (BBD) combined with response surface methodology (RSM). Three significant factors were studied: sucrose 9.9%, sorbitol 9.9%, and L-Arg 0.06 mol/L against virus titer of thermal-resistance of SVA as a response. The formulation improved the stability of SVA, whose viral infectivity titer decreased by 1.0 TCID₅₀/mL at 4°C, 25°C, and 37°C, respectively, until it decreased by 1.21 TCID₅₀/mL at 7 d of incubation at 42°C. The combinational thermal stabilizer generated in this study enabled the stabilization of the SVA, which might contribute to storage and transportation when the cold chain is unavailable, especially in rural areas. Therefore, the thermal stabilizer is an efficient candidate stabilizer for picornavirus formulations, which keep picornavirus infectivity at various temperatures. Further optimization of this approach will provide new opportunities for the generation of stabilizer formulation from different stabilizers.