Protective immunity induced by Tp0136 epitope vaccines with mRNA LNP or protein delivery

protective-immunity-induced-by-tp0136-epitope-vaccines-with-mrna-lnp-or-protein-delivery
Protective immunity induced by Tp0136 epitope vaccines with mRNA LNP or protein delivery

References

  1. Papp, J. R., Park, I. U., Fakile, Y., Pereira, L., Pillay, A. & Bolan, G. A. CDC laboratory recommendations for syphilis testing, United States,. Mmwr. Recommen. Rep. 73, 1–32 (2024).

    Google Scholar 

  2. Ramchandani, M. S., Cannon, C. A. & Marra, C. M. Syphilis. Infect. Dis. Clin. North Am. 37, 195–222 (2023).

    Google Scholar 

  3. Ghanem, K. G., Ram, S. & Rice, P. A. The modern epidemic of syphilis. N. Engl. J. Med 382, 845–54 (2020).

    Google Scholar 

  4. Zhou, S. & Chanderraj, R. What is syphilis?. JAMA 329, 1710 (2023).

    Google Scholar 

  5. The Past 70 Years in Control of Syphilis in China: Elimination and Responses to Resurgence. Chen, Xiang-Sheng; Jiang, Ting-Ting; Yin, Yue-Ping; More International Journal of Dermatology and Venereology. 3:193-197, December 2020.

  6. Peeling, R. W., Mabey, D., Chen, X. S. & Garcia, P. J. Syphilis. Lancet 402, 336–46 (2023).

    Google Scholar 

  7. Newman, L., Kamb, M., Hawkes, S., Gomez, G., Say, L., Seuc, A. et al. Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data. PLoS Med 10, e1001396 (2013).

    Google Scholar 

  8. Buonsenso, D., Raffaelli, F., Camporesi, A., Fiori, B., Ricci, R. & Romano, L. Neonatal outcomes of mothers with syphilis during pregnancy: a retrospective single center experience. Children (Basel) 12, 307 (2025).

    Google Scholar 

  9. Kojima, N., Konda, K. A. & Klausner, J. D. Notes on syphilis vaccine development. Front Immunol. 13, 952284 (2022).

    Google Scholar 

  10. Sankaran, M., Glidden, D. V., Kohn, R. P., Nguyen, T. Q., Bacon, O., Buchbinder, S. P. et al. Doxycycline postexposure prophylaxis and sexually transmitted infection trends. JAMA Intern Med. 185, 266–72 (2025).

    Google Scholar 

  11. Lynn, W. A. & Lightman, S. Syphilis and HIV: a dangerous combination. Lancet Infect. Dis. 4, 456–66 (2004).

    Google Scholar 

  12. Huang, J., Jiang, Y., Lin, W., Chen, R., Zhou, J., Guo, S. et al. Virulence and adhesion of the treponema pallidum nichols strain simultaneously decrease in a Continuous-Infection new zealand white rabbit model. ACS Infect. Dis. 9, 1221–31 (2023).

    Google Scholar 

  13. Carlson, J. A., Dabiri, G., Cribier, B. & Sell, S. The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. Am. J. Dermatopathol. 33, 433–60 (2011).

    Google Scholar 

  14. Waugh, S. & Cameron, C. E. Syphilis vaccine development: Aligning vaccine design with manufacturing requirements. Hum. Vaccin Immunother. 20, 2399915 (2024).

    Google Scholar 

  15. Avila-Nieto, C., Pedreno-Lopez, N., Mitja, O., Clotet, B., Blanco, J. & Carrillo, J. Syphilis vaccine: challenges, controversies and opportunities. Front Immunol. 14, 1126170 (2023).

    Google Scholar 

  16. Lafond, R. E. & Lukehart, S. A. Biological basis for syphilis. Clin. Microbiol. Rev. 19, 29–49 (2006).

    Google Scholar 

  17. Li, W., Luo, X., Zheng, X. Q., Li, Q. L., Li, Z., Meng, Q. Q. et al. Treponema pallidum protein Tp0136 promotes angiogenesis to facilitate the dissemination of Treponema pallidum. Emerg. Microbes Infect. 13, 2382236 (2024).

    Google Scholar 

  18. Li, Q. L., Li, W., Zheng, X. Q., Ye, W. M., Xu, Q. Y., Ke, W. J. et al. Screening the B- and T-cell epitope map of TP0136 and exploring their effect in a Treponema pallidum rabbit model. Biomed. Pharmacother. 167, 115628 (2023).

    Google Scholar 

  19. Xu, M., Xie, Y., Zheng, K., Luo, H., Tan, M., Zhao, F. et al. Two Potential syphilis vaccine candidates inhibit dissemination of treponema pallidum. Front Immunol. 12, 759474 (2021).

    Google Scholar 

  20. Li, Q., Tong, M., Liu, L., Lin, L., Lin, Y. & Yang, T. Effect of anti-TP0136 antibodies on the progression of lesions in an infected rabbit model. Int Immunopharmacol. 83, 106428 (2020).

    Google Scholar 

  21. Chentoufi, A. A., Ulmer, J. B., BenMohamed, L. Antigen delivery platforms for Next-Generation coronavirus vaccines. Vaccines (Basel) 13, https://doi.org/10.3390/vaccines13010030 (2024).

  22. Mantegazza, A. R., Magalhaes, J. G., Amigorena, S. & Marks, M. S. Presentation of phagocytosed antigens by MHC class I and II. Traffic 14, 135–52 (2013).

    Google Scholar 

  23. Cavazzini, D., Spagnoli, G., Mariz, F. C., Reggiani, F., Maggi, S., Franceschi, V. et al. Enhanced immunogenicity of a positively supercharged archaeon thioredoxin scaffold as a cell-penetrating antigen carrier for peptide vaccines. Front Immunol. 13, 958123 (2022).

    Google Scholar 

  24. Kiaie, S. H., Majidi, Z. N., Ahmadi, A., Bagherifar, R., Valizadeh, H., Kashanchi, F. et al. Recent advances in mRNA-LNP therapeutics: Immunological and pharmacological aspects. J. Nanobiotechnol. 20, 276 (2022).

    Google Scholar 

  25. Scorza, F. B., Pardi, N. New kids on the block: RNA-based influenza virus vaccines. Vaccines (Basel) 6, https://doi.org/10.3390/vaccines6020020 (2018).

  26. Schoenmaker, L., Witzigmann, D., Kulkarni, J. A., Verbeke, R., Kersten, G., Jiskoot, W. et al. MRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. Int. J. Pharm. 601, 120586 (2021).

    Google Scholar 

  27. Delgado, K. N., Montezuma-Rusca, J. M., Orbe, I. C., Caimano, M. J., La Vake, C. J., Luthra, A. et al. Extracellular loops of the treponema pallidum FadL orthologs TP0856 and TP0858 elicit IgG antibodies and IgG(+)-Specific B-Cells in the rabbit model of experimental syphilis. mBio 13, e163922 (2022).

    Google Scholar 

  28. Ferguson, M. R., Delgado, K. N., McBride, S., Orbe, I. C., La Vake, C. J., Caimano, M. J. et al. Use of Epivolve phage display to generate a monoclonal antibody with opsonic activity directed against a subdominant epitope on extracellular loop 4 of Treponema pallidum BamA (TP0326). Front Immunol. 14, 1222267 (2023).

    Google Scholar 

  29. Delgado, K. N., Caimano, M. J., Orbe, I. C., Vicente, C. F., La Vake, C. J., Grassmann, A. A. et al. Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities. PLoS Pathog. 20, e1012443 (2024).

    Google Scholar 

  30. Jiang, J., Xu, L., Wang, X., Wang, M., Cao, Y., Li, R. et al. A comprehensive strategy for the development of a multi-epitope vaccine targeting Treponema pallidum, utilizing heat shock proteins, encompassing the entire process from vaccine design to in vitro evaluation of immunogenicity. Front. Microbiol. 16, 1551437 (2025).

    Google Scholar 

  31. Gote, V., Bolla, P. K., Kommineni, N., Butreddy, A., Nukala, P. K. & Palakurthi, S. S. A comprehensive review of mRNA vaccines. Int. J. Mol. Sci 24, 2700 (2023).

    Google Scholar 

  32. Radolf, J. D. & Kumar, S. The Treponema pallidum Outer Membrane. Curr. Top. Microbiol Immunol. 415, 1–38 (2018).

    Google Scholar 

  33. Reid, T. B., Godornes, C., Campbell, V. L., Laing, K. J., Tantalo, L. C., Gomez, A. et al. Treponema pallidum periplasmic and membrane proteins are recognized by circulating and skin CD4+ t cells. J. Infect. Dis. 230, 281–92 (2024).

    Google Scholar 

  34. Hawley, K. L., Montezuma-Rusca, J. M., Delgado, K. N., Singh, N., Uversky, V. N., Caimano, M. J. et al. Structural modeling of the treponema pallidum outer membrane protein repertoire: a road map for deconvolution of syphilis pathogenesis and development of a syphilis vaccine. J. Bacteriol. 203, e8221 (2021).

    Google Scholar 

  35. Arroll, T. W., Centurion-Lara, A., Lukehart, S. A. & Van Voorhis, W. C. T-Cell responses to Treponema pallidum subsp. Pallidum antigens during the course of experimental syphilis infection. Infect. Immun. 67, 4757–63 (1999).

    Google Scholar 

  36. Delgado, K. N., Vicente, C. F., Hennelly, C. M., Aghakhanian, F., Parr, J. B., Claffey, K. P. et al. Development and utilization of Treponema pallidum expressing green fluorescent protein to study spirochete-host interactions and antibody-mediated clearance: Expanding the toolbox for syphilis research. mBio 16, e325324 (2025).

    Google Scholar 

  37. Sajid, A., Matias, J., Arora, G., Kurokawa, C., DePonte, K., Tang, X. et al. MRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Sci. Transl. Med 13, j9827 (2021).

    Google Scholar 

  38. Pine, M., Arora, G., Hart, T. M., Bettini, E., Gaudette, B. T., Muramatsu, H. et al. Development of an mRNA-lipid nanoparticle vaccine against Lyme disease. Mol. Ther. 31, 2702–14 (2023).

    Google Scholar 

  39. Lukehart, S. A., Molini, B., Gomez, A., Godornes, C., Hof, R., Fernandez, M. C. et al. Immunization with a tri-antigen syphilis vaccine significantly attenuates chancre development, reduces bacterial load, and inhibits dissemination of Treponema pallidum. Vaccine 40, 7676–92 (2022).

    Google Scholar 

  40. Rufli, T. Syphilis and HIV infection. Dermatologica 179, 113–7 (1989).

    Google Scholar 

  41. Magnuson, H. J., Thomas, E. W., Olansky, S., Kaplan, B. I., de Mello, L. & Cutler, J. C. Inoculation syphilis in human volunteers. Medicine 35, 33–82 (1956).

    Google Scholar 

  42. MacArthur, C. J. The 3Rs in research: a contemporary approach to replacement, reduction and refinement. Br. J. Nutr. 120, S1–7 (2018).

    Google Scholar 

  43. Urselli, F., Gomez, A., Gray, M. D., Cameron, C. E. & Taylor, J. J. Identification of antibodies induced by immunization with the syphilis vaccine candidate Tp0751. Vaccine 50, 126804 (2025).

    Google Scholar 

Download references