Anti‐ TP0136 Antibody Delayed Syphilis Wound Healing by Inhibiting Angiogenesis Through the VEGF ‐A Signaling Pathway: A Novel View in Nonhealing Syphilis Wounds

Syphilis typically begins with a painless ulcer in the early stage, and most lesions resolve spontaneously. However, spontaneous healing is not universally observed, and reports of nonhealing ulcers in syphilis patients have increased in recent years. Angiogenesis plays a critical role in the wound-healing process during syphilis infection, and our previous work showed that anti-TP0136 antibodies delay lesion repair. This study aimed to investigate the mechanism by which anti-TP0136 antibodies impair syphilis wound healing, with a particular focus on angiogenesis. Using a syphilitic rabbit model administered with subcutaneous anti-TP0136 antibodies, we demonstrated delayed wound closure and reduced angiogenesis in local lesions. The antibody titer correlated positively with lesion diameter. In vitro, anti-TP0136 antibodies inhibited migration and angiogenic activity in human microvascular endothelial cells. Transcriptome sequencing combined with cellular validation revealed that the VEGF-A signaling pathway plays a central role in this anti-angiogenic effect. Collectively, our findings indicate that anti-TP0136 antibodies markedly delay syphilis wound healing by suppressing angiogenesis through the VEGF-A pathway. This work provides new insights into the mechanisms underlying nonhealing syphilitic ulcers.