References
-
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).
-
Ramchandani, M. S., Cannon, C. A. & Marra, C. M. Syphilis. Infect. Dis. Clin. North Am. 37, 195–222 (2023).
-
Ghanem, K. G., Ram, S. & Rice, P. A. The modern epidemic of syphilis. N. Engl. J. Med 382, 845–54 (2020).
-
Zhou, S. & Chanderraj, R. What is syphilis?. JAMA 329, 1710 (2023).
-
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.
-
Peeling, R. W., Mabey, D., Chen, X. S. & Garcia, P. J. Syphilis. Lancet 402, 336–46 (2023).
-
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).
-
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).
-
Kojima, N., Konda, K. A. & Klausner, J. D. Notes on syphilis vaccine development. Front Immunol. 13, 952284 (2022).
-
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).
-
Lynn, W. A. & Lightman, S. Syphilis and HIV: a dangerous combination. Lancet Infect. Dis. 4, 456–66 (2004).
-
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).
-
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).
-
Waugh, S. & Cameron, C. E. Syphilis vaccine development: Aligning vaccine design with manufacturing requirements. Hum. Vaccin Immunother. 20, 2399915 (2024).
-
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).
-
Lafond, R. E. & Lukehart, S. A. Biological basis for syphilis. Clin. Microbiol. Rev. 19, 29–49 (2006).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
Radolf, J. D. & Kumar, S. The Treponema pallidum Outer Membrane. Curr. Top. Microbiol Immunol. 415, 1–38 (2018).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
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).
-
Rufli, T. Syphilis and HIV infection. Dermatologica 179, 113–7 (1989).
-
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).
-
MacArthur, C. J. The 3Rs in research: a contemporary approach to replacement, reduction and refinement. Br. J. Nutr. 120, S1–7 (2018).
-
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).
