Peptide-Based Therapeutic HPV Cancer Vaccine Synthesized via Bacterial Outer Membrane Vesicles

Haoqian Chen,1 Xiao Zheng,2,3 Lingjue Li,1 Lishuxin Huang,1 Weiwei Huang,2 Yanbing Ma2 1Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, People’s Republic of China; 2Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, People’s Republic of China; 3School of Life Sciences, Yunnan University, Kunming, People’s Republic of ChinaCorrespondence: Lishuxin Huang, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, 650504, People’s Republic of China, Tel/Fax +86 871 6592 6040, Email huanglishuxin19@163.com Yanbing Ma, Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, 650032, People’s Republic of China, Tel +86 871 6833 9287, Fax +86 871 6833 4483, Email yanbingma1969@126.comBackground: Peptide-based vaccines have broad application prospects because of their safety, simple preparation, and effectiveness, especially in the development of personalized cancer vaccines, which have shown great advantages. However, the current peptide-based vaccines often require artificial synthesis and intricate delivery technology, which increases the cost and complexity of preparation.Methods: Here, we developed a simple technique for combining a peptide and a delivery system using the natural secretion system of bacteria. Specifically, we biosynthesized an antigenic peptide in bacteria, which was then extracellularly released through the bacterial secretory vesicles, thus simultaneously achieving the biosynthesis and delivery of the peptide.Results: The system utilizes the natural properties of bacterial vesicles to promote antigen uptake and dendritic cell (DC) maturation. Therefore, tumor-specific CD4+ Th1 and CD8+ cytotoxic T lymphocyte (CTL) responses were induced in TC-1 tumor-bearing mice, thereby efficiently suppressing tumor growth.Conclusion: This research promotes innovation and extends the application of peptide-based vaccine biosynthesis technology. Importantly, it provides a new method for personalized cancer immunotherapy that uses screened peptides as antigens in the future.Keywords: tumor immunization, peptide vaccine, outer membrane vesicle, delivery system