P9: Process Fitting and Optimization of a Virus-like Particle Based Vaccine Production Platform

Virus-like particles (VLPs) have been successfully used as epitope carriers for therapeutic and prophylactic vaccine development for the last decade. Most of the VLP based vaccines clinically tested in humans have utilized VLPs derived from Allolevivirus Qbeta which is an RNA bacteriophage. Pfizer has licensed the Qbeta VLP technology from Cytos Biotechnology AG, Switzerland. This technology employs E. coli cells to recombinantly produce Qbeta virus coat protein monomers which self assemble into virus-like particles in the cytoplasm. At the end of a high cell density and high oxygen demand fermentation process cells are recovered and disrupted. The resulting cell slurry is clarified and purified through a capture chromatography. After the subsequent endotoxin and host cell protein removal and polishing steps the VLPs are conjugated to the target antigen via hetero-bifunctional chemical agents, such as SMPH. Technology transfer required challenging efforts for reassessment of equipment capabilities and process fitting. Nevertheless, a robust and reproducible platform for VLP-based vaccine production was implemented in Pfizer’s cGMP pilot plant. Clinical trial materials were sent for immunogenicity testing and Phase I clinical trials have started. Moreover, Pfizer is working on optimizing this platform further towards an improved commercial process with higher yields. This poster gives an overview of the process fitting and optimization efforts for Qbeta VLP fermentation platform.