Urea Improves Stability of Inactivated Polio Vaccine Serotype 3 During Lyophilization and Storage in Dried Formulations.

Stable formulations of inactivated polio vaccine (IPV) could reduce cold-chain requirements and increase distribution of the vaccine to developing countries. Recently, significant improvement in thermal stability of IPV vaccines has been achieved by including urea in lyophilized formulations. In the present study, we investigated the effects of urea on recovery of potency of IPV after lyophilization and storage at 37°C and the correlation of potency recovery with key biophysical properties of IPV. By dynamic light scattering and transmission light microscopy, we found that loss of potency appeared to be due to agglomeration of virus particles during lyophilization and that moderate concentrations (e.g., 0.4 M) of urea reduced agglomeration and improved potency recovery. In addition, the relative thermal stability of the viron proteins was assessed after rehydration with temperature-dependent intrinsic fluorescence. Lyophilization of formulations without urea and postdrying storage resulted in reduced apparent melting temperatures in rehydrated samples. In formulations with urea, the rehydrated samples had thermal transitions and melting temperatures that were similar to those observed in aqueous control samples. Overall, the results indicated that in IPV formulations, urea improved potency recovery by inhibiting viron particle agglomeration and reducing denaturation of viron proteins.