Disassembly mediated multimodal chromatography based purification of HPV-VLPs produced in Pichia pastoris

Human Papillomavirus Virus-Like Particles (HPV-VLPs) are a highly effective vaccine to prevent cervical cancer. Current production and purification processes for HPV-VLPs suffer from poor yield and suboptimal process economics. The current study presents a purification strategy based multi-modal cation exchange chromatography (Capto™ MMC) for the purification of HPV-VLPs produced in Pichia pastoris. Single step purification of disassembled VLPs offered a superior product recovery (> 80 %) and purity (> 70 %) compared to traditional VLP purification platforms that comprise anion exchange and cation exchange chromatography (yield: 32 %, purity: 52 %). Furthermore, it was observed that disassembling the intact VLPs to capsomere subunits before purification provided an improved dynamic binding capacity of up to 18.1 mg/mL (at 2 min residence time), 4 times higher than that with intact HPV-VLPs.