Background/Objectives: Virus-like particle (VLP) vaccines based on human papillomavirus (HPV) L1 proteins have high efficacy for preventing cervical cancer and other HPV-associated diseases. The production yields of commercial HPV VLPs remain suboptimal. We aimed to improve HPV VLP production efficiency using a hyper-expression vector system for the expression of L1 proteins of four major HPV serotypes—HPV 6, 11, 16, and 18. Methods: HPV L1 proteins were expressed in Trichoplusia ni (Hi5) insect cells via a hyper-expression baculovirus vector system. Following cell lysis using a microfluidizer, VLPs were purified through a two-step chromatographic process. Particle morphology was characterized using transmission electron microscopy and dynamic light scattering. Immunogenicity was evaluated using a murine model; mice received three intramuscular injections of the purified quadrivalent VLPs. The resulting IgG and neutralizing antibody responses were compared with those elicited by the commercial quadrivalent vaccine, Gardasil. Results: The L1 proteins from HPV 6, 11, 16, and 18 were successfully expressed at high levels in Hi5 cells, forming uniformly sized VLPs with hydrodynamic diameters of 50–60 nm. The average production yield of the quadrivalent VLPs exceeded 40 mg/L, an improvement over conventional yields. The candidate VLPs elicited strong HPV-specific IgG and neutralizing antibody responses in mice, comparable to those induced by Gardasil. Conclusions: The hyper-expression baculovirus vector system enables high-yield production of HPV L1 VLPs with desirable structural and immunogenic properties. This approach holds promise for the cost-effective and scalable manufacturing of next-generation HPV VLP vaccines, facilitating broader global access to HPV immunization.
Choi et al. (Thu,) studied this question.