Design of Epitopes from <i>Treponema pallidum</i> Lipoprotein Antigens for Syphilis Diagnosis and Treatment Prognosis

Syphilis, a multistage sexually transmitted infection, causes severe complications if untreated. Accurate diagnosis remains difficult due to the low protein content of <i>Treponema pallidum</i> and in vitro culture difficulty. Advances in immunoproteomics have identified key antigens that enhance diagnostic accuracy. Epitopes of immunodominant antigen proteins Tp0171, Tp0435, Tp0574, Tp0684, and Tp0453 were designed by bioinformatics tools, and mimetic peptides were chemically synthesized. A diagnostic accuracy cross-sectional study was performed to validate a prototype technology as a serodiagnosis platform for syphilis. Five peptides were used as antigens in a peptide-based ELISA against serum samples from syphilis-positive or noninfected patients (<i>n</i> = 122). CE<i>Tp</i>0435 achieved 100% sensitivity and specificity with a high accuracy. The peptides CE<i>Tp</i>0171 and CE<i>Tp</i>0574 demonstrated high diagnostic performance, with sensitivity above 83% and specificity >90%. Peptides CE<i>Tp</i>0684 and CE<i>Tp</i>0453 exhibited sensitivity above 80% and 90%, respectively; CE<i>Tp</i>0453 showed reduced specificity (∼66%). The peptides CE<i>Tp</i>0435 and CE<i>Tp</i>0171 maintained high diagnostic accuracy across syphilis stages, with a sensitivity above 83% and a specificity exceeding 97%. Peptides CE<i>Tp</i>0435 and CE<i>Tp</i>0171 effectively monitored syphilis treatment, as evidenced by the significant post-treatment decline in serum antibody levels, supporting their potential for evaluating the therapeutic efficacy. We obtained two epitopes mimetic peptides as advantageous antigens for serodiagnosis and treatment monitoring.