Increased Production of Nonenveloped Virus‐Like Particles in a Neutral pH‐Adapted Insect Cell Line

ABSTRACT Virus‐like particles (VLPs) are vaccine antigens that are actively being developed as vaccines because of their high immunogenicity and safety. Among the cell culture parameters for VLP production, pH can have a significant effect on VLP formation and stability. In this study, the pH of cultured insect cells (6.2) was adjusted to a neutral pH, and the effect on VLP production was evaluated. A neutral pH‐adapted High Five insect cell line was established and named HF7. Compared with parent High Five cells, HF7 cells were approximately 2 μm larger and showed approximately sixfold greater viral replication. The production of nonenveloped VLPs in HF7 cells was evaluated using enterovirus 71 (EV‐71), porcine parvovirus (PPV), porcine circovirus Type 2 (PCV2), and canine parvovirus (CPV) VLPs. As a result, increased production of all VLPs and VLP formation were confirmed. However, the increased production of VLPs is thought to be due to increased cell metabolism and virus replication rather than the formation or stability of VLPs. The neutral pH‐adapted HF7 cell line established in this study can be utilized to increase the production of various recombinant proteins, including VLPs.