Stabilization study of inactivated foot and mouth disease virus vaccine by size-exclusion HPLC and differential scanning calorimetry.
The inactivated foot and mouth disease virus (FMDV), which has a sedimentation coefficient of 146S, is crucial to the efficacy of vaccine preparations, but extremely unstable in vitro. It is prone to dissociate into smaller particles referred to as 12S with a concomitant decrease in immunogenicity; therefore, it is of great importance to find the best condition for stabilizing the FMDV. In the present work, the effects of solution pH and temperature on the dissociation of 146S was investigated and potential stabilizers were screened, with aid of high-performance size-exclusion chromatography (HPSEC) for rapid and quantitative determination of 146S, together with differential scanning calorimetry (DSC) technology for thermal stability analysis. The most stable pH was found between 7.5 and 8.0. Among excipients tested, sucrose and glycerol provided the best protection, such that the half-life of 146S in solution at 45°C could be prolonged from less than 30min to more than 3days by adding 20% sucrose. The stabilization mechanism was confirmed using DSC analysis, which showed that the transition temperature related to 146S dissociation was increased by 5.4°C in the presence of 20% sucrose. The physical stabilization effects afforded by these stabilizers would allow for the retaining of effective 146S antigens during transportation and storage under relative harsh condition.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
Yanli
Y
Yang
China Institute of Veterinary Drug Control, Beijing 100081, PR China.
Qizu
Q
Zhao
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Zhengjun
Z
Li
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
Lijing
L
Sun
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
Guanghui
G
Ma
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address: spzhang@ipe.ac.cn.
Songping
S
Zhang
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address: zgsu@ipe.ac.cn.
Zhiguo
Z
Su
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D004355:Drug Stability; D005079:Excipients / Q000378:metabolism*; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D006863:Hydrogen-Ion Concentration; D013696:Temperature; D015164:Vaccines, Inactivated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D005079:Excipients; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
Dissociation; Excipient; Foot and mouth disease virus; Stabilization; Thermal stability