Teh-Poot Christian F, Alfaro-Chacón Andrea, Pech-Pisté Landy M, Rosado-Vallado Miguel E, Asojo Oluwatoyin Ajibola, Villanueva-Lizama Liliana E, Dumonteil Eric, Cruz-Chan Julio Vladimir
Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, Mérida 97000, Mexico.
Department of Chemistry and Biochemistry, Hampton University, Hampton, VA 23668, USA.
Pathogens. 2025 Apr 3;14(4):342. doi: 10.3390/pathogens14040342.
Chagas disease, caused by the protozoan (), is the most significant neglected tropical disease affecting individuals in the Americas. Currently, available drugs, such as nifurtimox and benznidazole (BZN), are both toxic and ineffective in the chronic phase of the disease. A promising alternative is the development of a Chagas disease vaccine, although this effort is hampered by the complexity of the parasite and HLA polymorphisms. In addition, the activation of epitope-specific CD8 T cells is critical to conferring a robust cell-mediated immune response and protection by producing IFN-γ and perforin. Thus, the antigen (s) for the development of a Chagas vaccine or immunotherapy must include CD8 T cell epitopes. In this study, we aimed to develop a multi-epitope recombinant protein as a novel human vaccine for Chagas disease. Sixteen database programs were used to predict 40 potential epitopes for the HLA-A02:01 allele. Nine out of the 40 predicted epitopes were able to elicit IFN-γ production in Peripheral Blood Mononuclear Cells (PBMCs) from Chagas patients. Molecular docking revealed a good binding affinity among the epitopes with diverse HLA molecules. Therefore, a recombinant multi-epitope protein including these nine CD8 epitopes was expressed and demonstrated to recall an antigen-specific immune response in assays using PBMCs from Chagas patients with the HLA-A02 allele. These findings support the development of this multi-epitope protein as a promising candidate human vaccine against Chagas disease.
恰加斯病由原生动物（此处原文未给出具体名称）引起，是影响美洲人群的最严重的被忽视热带病。目前，可用药物如硝呋莫司和苯硝唑（BZN）在该病的慢性期既有毒性又无效。一种有前景的替代方法是开发恰加斯病疫苗，尽管这一努力因寄生虫的复杂性和HLA多态性而受阻。此外，表位特异性CD8 T细胞的激活对于通过产生干扰素-γ和穿孔素赋予强大的细胞介导免疫反应和保护至关重要。因此，用于开发恰加斯病疫苗或免疫疗法的抗原必须包括CD8 T细胞表位。在本研究中，我们旨在开发一种多表位重组蛋白作为新型恰加斯病人类疫苗。使用16个数据库程序预测了HLA-A02:01等位基因的40个潜在表位。40个预测表位中有9个能够在恰加斯病患者的外周血单核细胞（PBMC）中引发干扰素-γ的产生。分子对接显示这些表位与多种HLA分子之间具有良好的结合亲和力。因此，表达了一种包含这9个CD8表位的重组多表位蛋白，并在使用具有HLA-A02等位基因的恰加斯病患者的PBMC进行的检测中证明其能唤起抗原特异性免疫反应。这些发现支持将这种多表位蛋白开发为一种有前景的抗恰加斯病人类疫苗候选物。
