Lyophilization and the Thermostability of Vaccines

Currently, vaccines are developed as either lyophilized or aqueous formulations; however, the inherent lack of vaccine thermostability requires storage at subambient temperatures. In the developing world, meeting these storage requirements can be difficult, and, as a result, vaccines are often exposed to temperatures that cause losses in vaccine efficacy. The current lack of vaccines that possess sufficient thermostability is therefore a significant barrier to global vaccination efforts. Although lyophilization and stabilizing excipients have conferred marginal stability on many vaccines, the development of adequately thermostable vaccines has historically been hindered by the inherent lability and complex nature of vaccine entities. Thus, with few exceptions, reasons for vaccine activity loss are not well understood. This review describes common mechanisms of vaccine component degradation, as well as methods used to stabilize vaccines with particular emphasis on lyophilization. The application of biophysical techniques to characterize complex vaccine components and their potential role in the future development of more thermostable vaccines is also discussed.