Evaluation of the Thermal Stability of Gardasil®

Abstract

The thermostability of GARDASIL® (Merck & Co., Inc, Whtehouse Station, NJ, USA), a developmental vaccine against human papillomavirus (HPV), was evaluated using an enzyme immunoassay, referred to as the in vitro relative potency (IVRP) assay anddifferential scanning calorimetry (DSC). Gardasil samples were stored at temperatures ranging from 4 to 42 °C and tested for IVRP at various time points. Extrapolation of the IVRP results indicates GARDASIL is extremely stable. The half-life of the vaccine isestimated to be 130 months or longer at temperatures up to 25 °C. At 37 ºC, the half-life is predicted to be 18 months and at 42 ºC, the half-life is predicted to be approximately 3 months. Differential scanning calorimetry (DSC) analysis was used to evaluate the process of protein denaturation during a rapid temperature increase (as opposed to longterm storage at a specific temperature). Differences were seen among the DSC profiles of the four HPV types tested. This indicates that small differences in the amino acid structure can have a significant effect on the intermolecular contacts that stabilize the L1 proteins and the VLP assembly. For the Gardasil samples evaluated here, DSC results demonstrated the relative overall structural stability of the VLPs, but were not predictive of the excellent long-term stability observed with the IVRP assay.