Stability study of recombinant 9-valent human papillomavirus vaccine based on Escherichia coli expression system.

Abstract

This study reports on the long-term stability of a recombinant 9-valent HPV vaccine, addressing a gap in the literature as previous research did not extend beyond 72 months. The vaccine targets HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and was produced using an E. coli expression system. We optimized soluble HPV L1 protein expression by truncating the N- and C-termini, resulting in HPV L1 virus-like particles (VLPs). Structural analysis confirmed the VLPs' resemblance to natural ones, suitable for vaccine production. Stability testing encompassed appearance, dosage, pH, osmolarity, aluminum content, polysorbate 80, in vitro relative potency, abnormal toxicity, in vivo potency, sterility, and endotoxin levels. The vaccine showed stability under extreme conditions of light (4500 lx) and shaking table vibration (10-30 rpm) for at least 7 days at 5 ± 3°C. Long-term storage at 5 ± 3°C maintained stability for up to 72 months, while accelerated testing at 25 ± 2°C showed stability for at least 12 months. The findings suggest that the vaccine's potency is best preserved under protection from high temperatures and direct light, with even harsh conditions not significantly compromising stability. This enhances the global distribution potential of the HPV vaccine.