Advancements in Syphilis Vaccine Development

In the last decade, we have witnessed outstanding scientific advances towards the development of a globally efficacious syphilis vaccine. This manuscript summarizes information presented at the Shanghai International Syphilis Symposium (October 20–22, 2025, Shanghai, China) during the Vaccine Development session. Dr. Lorenzo Giacani (University of Washington) moderated the session. Dr. Justin Radolf (UConn Health) summarized key historical research findings that inform modern vaccine development, emphasizing how protective immunity was demonstrated in the early days of syphilis vaccine research and attributed to antibodies. Drs. Caroline Cameron (University of Victoria), Melissa Caimano (UConn Health), and Feijun Zhao (University of South China) discussed their research relating to antigen selection, identification of potentially protective B cell epitopes, results of immunization/challenge experiments, vaccine delivery platforms, and manufacturing requirements, with particular emphasis on the development of chimeric vaccine candidates. While challenges remain, the application of high-throughput immunological, proteomic, and genomic techniques discussed here has revealed surface-exposed epitopes of TPA outer membrane proteins with promising, but as yet unproven, vaccine potential. Multiple vaccine designs have emerged as options to efficiently and effectively package these epitopes in chimeric structures and platforms that can meet manufacturing standards and requirements. Efforts are also ongoing to identify and procure clinically approved adjuvants to be delivered alongside vaccine candidates.