title: Evaluation of the thermal stability of Gardasil.
abstract: The thermostability of GARDASIL (Merck & Co., Inc, Whitehouse 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 and differential scanning calorimetry (DSC). Gardasil samples were stored at temperatures ranging from 4 to 42 degrees 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 is estimated to be 130 months or longer at temperatures up to 25 degrees C. At 37 degrees C, the half-life is predicted to be 18 months and at 42 degrees C, the half-life is predicted to be approximately three months. Differential scanning calorimetry (DSC) analysis was used to evaluate the process of protein denaturation during a rapid temperature increase (as opposed to long-term 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.
authors.affiliation: Merck Research Laboratories Department of Bioprocess, West Point, Pennsylvania, USA. Li_Shi@merck.com
authors.forename: Mary L
authors.initials: ML
authors.lastname: Shank-Retzlaff
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Carrie
authors.initials: C
authors.lastname: Anderson
authors.forename: Melissa
authors.initials: M
authors.lastname: Hamm
authors.forename: Katrina
authors.initials: K
authors.lastname: High
authors.forename: Mai
authors.initials: M
authors.lastname: Nguyen
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Washabaugh
authors.forename: Robert
authors.initials: R
authors.lastname: Sitrin
authors.forename: Li
authors.initials: L
authors.lastname: Shi
mesh_terms: D002152:Calorimetry, Differential Scanning; D006207:Half-Life; D006358:Hot Temperature; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines / Q000592:standards*; D014771:Virion / Q000502:physiology
chemical_list: D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines