Designing a novel multiepitope vaccine candidate against Treponema pallidum via adhesins using reverse vaccinology

Abstract

Abstract Syphilis, caused by Treponema pallidum ( T. pallidum ), represents a significant worldwide public health threat. This spiral-shaped, Gram-negative pathogen is a strict human-specific obligate parasite primarily transmitted through sexual contact. This pathogen induces a multistage and multisystem progressive disease, against which no effective prophylactic vaccine currently exists. This study focuses on syphilis prevention and control by employing a reverse vaccinology approach to investigate the immunogenic properties of T. pallidum adhesin proteins. Fifteen T-cell epitopes and seven B-cell epitopes were screened and linked in series using appropriate linkers to construct a multi-epitope vaccine. The vaccine was subjected to in silico analysis, including secondary and tertiary structure prediction, molecular docking, and molecular dynamics simulation. Based on these analyses, a recombinant plasmid, pET-28a(+)-MEVTP, was constructed, and the purified recombinant protein was obtained via nickel column affinity chromatography. In silico immune simulation results suggested that the vaccine could induce specific cellular and humoral immune responses. However, further experimental evaluation of its immunological effects is required to validate the computationally predicted immunogenicity, thereby establishing an experimental basis for its advancement toward translational medical applications and providing critical evidence to support syphilis prevention and control efforts.