Treponema pallidum mRNA-LNP vaccine candidate encoding TP0954 induces strongly protective immunity in rabbits

Introduction Syphilis is a sexually or vertically transmitted disease caused by the infection of Treponema pallidum ( T. pallidum ). Syphilis prevalence has risen globally despite the availability of effective treatments. The development of a syphilis vaccine is crucial for controlling disease spread and severity. Over the decades, a variety of strategies have been examined including inactivated bacteria, subunit recombinant proteins and DNA vaccines, some of which showed promising results. Recent years, mRNA vaccines have become next-generationapproaches against infectious diseases. Methods In this study, we successfully constructed a TP0954 mRNA vaccine and confirmed the immunogenicity of the mRNA vaccine in BALB/c mice and New Zealand White (NZW) rabbits. Then the protective immunity was assessed in immunized NZW rabbits. Results Our mRNA vaccine elicited humoral and cellular immunological responses both in BALB/c mice and NZW rabbits. Moreover, TP0954 mRNA vaccine was more effective in attenuating lesion development compared with TP0954 protein vaccine. Similarly, the T. pallidum burdens at the challenge sites and distal organs in rabbits immunized with TP0954 mRNA vaccine were lower compared with TP0954 recombinant protein vaccine. Conclusion Therefore, we successfully constructed a novel mRNA vaccine targeting TP0954 for syphilis and found superior immune protective effects compared with TP0954 recombinant protein vaccine, further confirming that TP0954 is a promising vaccine candidate for syphilis.