Effects of Freezing on Vaccine Potency

Hepatitis B Diminsky D, Moav N, Gorecki M, Barenholz Y. Physical, chemical and immunological stability of CHO-derived hepatitis B surface antigen (HBsAg) particles. Vaccine 1999;18:3-17. Recombinant hepatitis B surface antigen were stored at various conditions for 12-18 months in the naked form (HBsAg) or adsorbed to alum (HBV vaccine). HBsAg particles fully retained the original peptide composition when stored for 6 months, as a dispersion, at -20°C and 4°C; and as lyophilized powder at -20°C, 4°C, room temperature and 37°C. HBV immunogenicity was evaluated according to dose-dependent changes in antibody titers in immunized mice. The HBV vaccine ED50 for achieving seroconversion was 0.07 microg/ml/mouse, indicating that the vaccine is very immunogenic. However, freezing or freeze-drying of the HBV vaccine resulted in the total loss of vaccine immunogenicity (in spite of the good chemical stability). Yet full HBV vaccine immunological potency was retained for at least 2.5 years at 4°C. In conclusion, the HBV vaccine (but not naked HbsAg particles) lost its immunological potency upon freezing or freeze drying. The authors suggest that the HBV vaccine's physical, chemical and immunological characteristics are sufficiently stable at high temperatures to reduce the need for cold chain transportation.