An Adenoviral-Vectored Tp0326 Vaccine Elicits Robust Functional Antibodies to Prevent Treponema pallidum Dissemination in a Rabbit Model.

Vaccination can prevent congenital infections by inducing antibodies that block transplacental pathogen transmission. For syphilis, which is caused by Treponema pallidum (T. pallidum), no vaccine is yet available to halt its vertical spread to fetuses. Here, we designed an adenovirus-vectored vaccine expressing the T. pallidum outer membrane protein TP0326 and evaluated its immunogenicity and protective efficacy in animal models. The vaccine elicited robust humoral and Th2‑biased cellular immune responses in both mice and rabbits, with resulting antibodies exhibiting potent anti‑adhesion, opsonophagocytic, and bactericidal activities. In rabbits challenged with high- or low-dose T. pallidum, vaccination significantly reduced lesion severity and tissue bacterial burden, while enhancing local phagocytic responses. Intramuscular immunization promoted early opsonophagocytosis and restricted pathogen dissemination by rabbit infectivity test. These findings demonstrate that the TP0326 based adenovirus vaccine induces functional antibody‑mediated immunity and supports its further development as a candidate vaccine for preventing congenital syphilis.