Screening helper T lymphocyte epitopes based on IFN-γ/IL-10 ratio for developing a novel multi-epitope vaccine candidate using Wolbachia surface protein as an adjuvant against visceral leishmaniasis

作者：Jianhui Zhang, Tianhang Lv, Shuoyan Tan, Yu LingQi, Yangjian Chi, Jianping Chen, Xiaohui Fan, Xiaoyan Lu · 发表于：Parasites & Vectors · 年份：2025 · DOI：10.1186/s13071-025-06756-5 · 被引用次数：5 · 研究领域：vaccines and immunoinformatics approaches、Research on Leishmaniasis Studies、Monoclonal and Polyclonal Antibodies Research

BACKGROUND: Visceral leishmaniasis (VL) is the most lethal form of leishmaniasis. In terms of anti-leishmanial vaccines, favorable immune responses are Th1 responses that primarily produce interferon gamma (IFN-γ) and activate macrophages for leishmanicidal effects. The selection of IFN-γ-inducing epitopes in silico may reduce the steps of pre-clinical evaluation and increase the certainty of the better-designed vaccine. Wolbachia surface protein (WSP) derived from Wolbachia bacteria that have been reported to reside in sandflies can trigger TLR2 and TLR4 activation to favor Th1 immune responses, which may serve as a potential adjuvant candidate for the Leishmania vaccine. Therefore, in this study, helper T lymphocyte epitopes that may induce favorable immune responses were identified, and WSP was served as an adjuvant to design a novel multi-epitope vaccine candidate. METHODS: Leishmania hemoglobin receptor (HbR), kinetoplastid membrane protein-11 (KMP-11), glycoprotein of 63 kDa (Gp63), thiol-specific antioxidant antigen (TSA), and sterol 24-c-methyltransferase (SMT) were analyzed by immunoinformatics to screen helper T lymphocyte and cytotoxic T lymphocyte epitopes. The antigenicity, toxicity, allergenicity, and IFN-γ-inducing epitope potential of T epitopes were predicted. The immune simulation was performed to calculate IFN-γ/interleukin (IL)-10 ratios to predict the immune responses induced by the helper T lymphocyte epitopes. Molecular docking and molecular dynamics si...