Real-time stability of a hepatitis E vaccine (Hecolin®) demonstrated with potency assays and multifaceted physicochemical methods. Issue 48 (21st November 2016)

• Record Type: Journal Article
• Authors: Zhang, Xiao; Wei, Minxi; Sun, Guang; Wang, Xin; Li, Min; Lin, Zhijie; Li, Zhongyi; Li, Yufang; Fang, Mujin; Zhang, Jun; Li, Shaowei; Xia, Ningshao; Zhao, Qinjian
• Is Part Of: Vaccine. Volume 34:Issue 48(2016)
• Page Start: 5871
• Page End: 5877
• Publication Date: 2016-11-21
• Subjects: Neutralizing epitope -- Hepatitis E virus -- Hepatitis E vaccine -- Monoclonal antibody -- In vivo mouse potency -- In vitro relative potency (IVRP) -- Real-time stability; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.10.045
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Mouse potency of Hecolin® in final container form met the 24 Mo specifications. The antigen integrity was confirmed in adjuvanted form during storage. Particle characteristics were unaltered during real time stability assessment. No alteration in antigen thermal stability in the prefilled syringes was observed. Antigen immunoreactivity to a panel of mAbs remained unchanged during storage. Particle structure and epitope integrity was maintained in post storage syringes. Abstract: The first prophylactic vaccine against hepatitis E virus (HEV), Hecolin®, was licensed in China. Recombinant p239 virus-like particle (VLP) is its active component with dimeric protein as the basic building block harboring the immuno dominant and neutralizing epitopes. The real time and real condition stability of the prefilled syringes for the vaccine was demonstrated using both in vivo mouse potency and in vitro antigenicity assays. A total of 12 lots of Hecolin® were assessed with a set of assays after storage at 2–8 °C for 24 months. The particle characteristics of p239 VLP recovered from the aluminum-containing adjuvant was assessed with different methods including analytical ultracentrifugation, high performance size exclusion chromatography and transmission electron microscopy. The thermal and conformational stability of the adsorbed antigen was assessed using differential scanning calorimetry. The protein integrity of the recovered p239 antigen was demonstrated using SDS-PAGE with silvering staining, LC-MS and MALDI-TOF MS. Most importantly, the binding activity to the neutralizing antibody or vaccine antigenicity was measured using an epitope-specific and real-time SPR assay and a monoclonal antibody-based sandwich ELISA. Taken together, the overall good stability of the Hecolin® prefilled syringes was demonstrated with unaltered molecular and functional attributes after storage at 2–8 °C for 24 months.