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

Zhiyu Lu¹Yizhou Lu²Di Liu²Fangzhi Du¹Qingyun Wu¹Guoyang Liao³Yanan Wu³Ruili Zhang^2*Jian Zhou^3*Qian-Qiu Wang^1*

• ¹Affiliated Hospital for Skin Diseases of Chinese Academy of Medical Sciences, Nanjing, China
• ²Department of Dermatology, The Second Affliated Hospital of Nanjing Medical University, Nanjing, China
• ³Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Medical Biology, Kunming, China

Abstract 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-generation approaches against infectious diseases. 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. 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. 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.