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Human vaccines & immunotherapeutics
Dec, 2025;21 (1): 2455807.

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

Yuying Liu, Dan Chen, Li Zhao, Haijiang Zhang, Shuming Wu, Xiao Chen, Ercui Shen, Ling Li, Zengmin Yang, Yan Wang, Fei Yin, Yao Zhang, Yazheng Shi, Shuyi Zhou, Shuang Li, Xiaoli Du, Jiaping Guo, Di Wang, Huan Wang, Shujuan Liu, Guiying Jin, Hongcai Zhang, Xinyu Yu, Xuejiao Chen, Lulu Shang, Yang Liu, Yongjiang Liu
Author Information
  1. Yuying Liu: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China. ORCID
  2. Dan Chen: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  3. Li Zhao: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  4. Haijiang Zhang: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  5. Shuming Wu: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  6. Xiao Chen: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  7. Ercui Shen: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  8. Ling Li: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  9. Zengmin Yang: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  10. Yan Wang: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  11. Fei Yin: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  12. Yao Zhang: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  13. Yazheng Shi: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  14. Shuyi Zhou: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  15. Shuang Li: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  16. Xiaoli Du: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  17. Jiaping Guo: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  18. Di Wang: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  19. Huan Wang: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  20. Shujuan Liu: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  21. Guiying Jin: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  22. Hongcai Zhang: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  23. Xinyu Yu: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  24. Xuejiao Chen: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  25. Lulu Shang: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  26. Yang Liu: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China.
  27. Yongjiang Liu: R&D Center, Beijing Health Guard Biotechnology Inc., BDA, Beijing, China. ORCID
PMID: 39973250 DOI: 10.1080/21645515.2025.2455807

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 expression system. We optimized soluble HPV L1 protein expression by truncating the - 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, relative potency, abnormal toxicity, 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.

Keywords

Escherichia coli recombinant 9-valent human papillomavirus vaccine vaccine stability

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MeSH Term

Papillomavirus Vaccines
Escherichia coli
Vaccines, Synthetic
Drug Stability
Capsid Proteins
Humans
Animals
Oncogene Proteins, Viral
Papillomavirus Infections
Female
Vaccines, Virus-Like Particle
Gene Expression
Temperature
Vaccine Potency
Mice
Drug Storage

Chemicals

Papillomavirus Vaccines
Vaccines, Synthetic
Capsid Proteins
Oncogene Proteins, Viral
HPV L1 protein, Human papillomavirus
Vaccines, Virus-Like Particle
Journal Article

Word Cloud

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