Immunization with Tp0954, an adhesin of Treponema pallidum, provides protective efficacy in the rabbit model of experimental syphilis.

Syphilis, a chronic multisystemic disease caused by spirochete Treponema pallidum subspecies pallidum infection, continues to be a serious global health problem and congenital syphilis remains a major cause of adverse outcomes in pregnancy in developing countries. The development of an effective vaccine is the most cost-effective way to eliminate syphilis, but so far has been elusive. Here, we evaluated the immunogenicity and protective efficacy of Tp0954, a T. pallidum placental adhesin, as a potential vaccine candidate in a New Zealand White rabbit model of experimental syphilis. Animals immunized with recombinant Tp0954 (rTp0954) produced high titers of Tp0954-specific serum IgG, high levels of IFN-γ from splenocytes and specific splenocyte proliferation response when compared to control animals immunized with PBS and Freund's adjuvant (FA). Furthermore, rTp0954 immunization significantly delayed the development of cutaneous lesions, promoted inflammatory cellular infiltration at the primary lesion sites, as well as inhibited T. pallidum dissemination to distal tissues or organs when compared with that of the control animals. In addition, the naïve rabbits receiving popliteal lymph nodes from Tp0954-immunized, T. pallidum-challenged animals were not infected by T. pallidum, confirming sterile immunity. These findings suggest that Tp0954 is a potential vaccine candidate against syphilis.

Assessment of recombinant antigens Tp0100 and Tp1016 of Treponema pallidum for serological diagnosis of syphilis.

OBJECTIVE: To discover novel serodiagnostic candidates for the serological diagnosis of syphilis. METHODS: Two recombinant Treponema pallidum proteins Tp0100 and Tp1016 were expressed, purified, and identified by Western Blotting. A total of 600 clinical serum samples were tested with the Tp0100-based ELISA, the Tp1016-based ELISA, and the commercial LICA Syphilis TP kit (ChIVD, Beijing, China). The sensitivities were determined by testing 340 samples from individuals with clinically diagnosed primary, secondary, latent, and tertiary syphilis. The specificities were determined by screening 260 samples from healthy controls and individuals with potentially cross-reactive infections, including leptospirosis, Lyme disease, hepatitis B, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus. Kappa (κ) values were applied to compare the agreement between clinical syphilis diagnosis and the Tp0100-based ELISA, the Tp1016-based ELISA, or the LICA Syphilis TP test. RESULTS: Using clinical syphilis diagnosis as the gold standard, Tp0100 exhibited an overall sensitivity of 95.6% and specificity of 98.1% for testing IgG antibody while Tp1016 demonstrated only an overall sensitivity of 75.0% and specificity of 79.6%. In contrast, the LICA Syphilis TP test revealed an overall sensitivity of 97.6% and specificity of 96.2%. In addition, the overall percent agreement and corresponding κ values were 96.7% (95% CI 95.6%-97.8%) and 0.93 for the Tp0100-based ELISA, 77.0% (95% CI 74.3%-79.7%) and 0.54 for the Tp1016-based ELISA, and 97.0% (95% CI 96.0%-98.0%) and 0.94 for the LICA Syphilis TP test, respectively. CONCLUSION: The recombinant T. pallidum protein Tp0100 shows promise as a novel diagnostic antigen in the serological tests for syphilis.

A comparison of genotyping tool in Treponema pallidum: Review and meta-analysis.

BACKGROUND: To decipher the molecular epidemiology of the Treponema pallidum subspecies, pallidum, researchers have developed different molecular typing schemes which identify strains type from clinical specimens. However, the results of these studies show remarkable diversity. METHODS: We searched for literature in PubMed, MEDLINE, Web of Sciences, and OVID from January 1998 to January 2019, in order to compare the efficiency of typing schemes using published evidence for systematic reviews and meta-analyses. RESULTS: From the 43 studies included, the overall typing efficiency of Treponema pallidum was 71.4% (95% CI: 63.2-78.9%). Subgroup analyses indicated that the typing efficiency of CDC-typing (CDCT, 68.2%, 95% CI: 53.6-81.2%) was worse than those of enhanced CDC-typing (ECDCT, 72.3%, 95% CI: 60-83.1%), CDC-rspA (81.6%, 95% CI: 76.1-86.6%), multi-locus sequence typing (MLST, 67.1%, 95% CI: 61.1-72.7), and sequencing-based molecular typing (SBMT, 71.6%, 95% CI: 50-89.2%). A limitation of this review is that the studies included employed different criteria to collect and investigate samples of Treponema pallidum, which could contribute to heterogeneity. CONCLUSIONS: This analysis suggests that CDCT is an inferior scheme in molecular typing, the discriminatory power was very similar for ECDCT and SBMT. Other factors contributing to the heterogeneity between typing studies warrants further study.