Affinity chromatography for virus-like particle manufacturing: Challenges, solutions, and perspectives.

The increasing medical application of virus-like particles (VLPs), notably vaccines and viral vectors, has increased the demand for commercial VLP production. However, VLP manufacturing has not yet reached the efficiency level achieved for recombinant protein therapeutics, especially in downstream processing. This review provides a comprehensive analysis of the challenges associated with affinity chromatography for VLP purification with respect to the diversity and complexity of VLPs and the associated upstream and downstream processes. The use of engineered affinity ligands and matrices for affinity chromatography is first discussed. Although several representative affinity ligands are currently available for VLP purification, most of them have difficulty in balancing ligand universality, ligand selectivity and mild operation conditions. Then, phage display technology and computer-assisted design are discussed as efficient methods for the rapid discovery of high-affinity peptide ligands. Finally, the VLP purification by affinity chromatography is analyzed. The process is significantly influenced by virus size and variation, ligand type and chromatographic mode. To address the updated regulatory requirements and epidemic outbreaks, technical innovations in affinity chromatography and process intensification and standardization in VLP purification should be promoted to achieve rapid process development and highly efficient VLP manufacturing, and emphasis is given to the discovery of universal ligands, applications of gigaporous matrices and platform technology. It is expected that the information in this review can provide a better understanding of the affinity chromatography methods available for VLP purification and offer useful guidance for the development of affinity chromatography for VLP manufacturing in the decades to come.