Buruli ulcer is an emerging tissue-necrosis infectious disease, caused by the pathogen Mycobacterium ulcerans, leading to permanent deformity if untreated. Despite this debilitating condition, no specific disease-modifying therapeutics or vaccination is available to date. Therefore, we aimed to design an effective multi-epitope vaccine against M. ulcerans using vaccinomics approach. Briefly, the highest antigenic PE-PGRS protein was selected from which the promiscuous T- and B-cell epitopes were predicted. After rigorous assessment, 15 promising T- and B-cell epitopes were selected. The identified T-cell epitopes showed marked interactions towards their HLA-binding alleles and provided 99.8 % world population coverage. Consequently, a vaccine chimera was designed by connecting these epitopes with suitable linkers and LprG adjuvant. The vaccine construct was highly antigenic, immunogenic and non-allergenic; hence, subjected to homology modelling. The molecular docking and dynamics simulation revealed a strong and stable interaction between vaccine and toll-like receptor 2. The binding energy and dissociation constant were -15.3 kcal/mol and 5.9 × 10-12 M, respectively. The computer-simulated immune responses showed abundance of immunoglobulins, increased interferon-γ production, and macrophages activation which are crucial for immune response against M. ulcerans. Furthermore, disulfide bridging and in silico cloning were also performed. These results suggest that the vaccine, if validated experimentally, will be a promising candidate against M. ulcerans and prevent Buruli ulcer disease.

中文翻译：

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溃疡分枝杆菌PE-PGRS家族蛋白的多肽疫苗的结构基础和设计-综合免疫学方法。

布鲁氏溃疡是一种新出现的组织坏死性传染病，由病原性溃疡分枝杆菌引起，如果不治疗会导致永久性畸形。尽管有这种令人衰弱的状况，但迄今为止尚无可改善疾病的特定疗法或疫苗接种。因此，我们旨在使用疫苗学方法设计一种有效的针对溃疡分枝杆菌的多表位疫苗。简而言之，选择最高抗原的PE-PGRS蛋白，从中预测混杂的T细胞和B细胞表位。经过严格的评估，选择了15种有希望的T细胞和B细胞表位。鉴定出的T细胞表位显示出与其HLA结合等位基因的显着相互作用，并提供了99.8％的世界人口覆盖率。因此，通过将这些表位与合适的接头和LprG佐剂连接来设计疫苗嵌合体。疫苗构建体具有高度抗原性，免疫原性和非过敏性。因此，要进行同源性建模。分子对接和动力学模拟揭示了疫苗与收费型受体2之间的强而稳定的相互作用。结合能和解离常数分别为-15.3 kcal / mol和5.9×10-12M。计算机模拟的免疫反应显示出丰富的免疫球蛋白，增加的干扰素-γ产生和巨噬细胞活化，这对于针对溃疡分枝杆菌的免疫反应至关重要。此外，还进行了二硫键桥接和计算机克隆。这些结果表明，如果通过实验验证，该疫苗将是抗溃疡分枝杆菌并预防布鲁氏溃疡病的有前途的候选药物。进行同源建模。分子对接和动力学模拟揭示了疫苗与收费型受体2之间的强而稳定的相互作用。结合能和解离常数分别为-15.3 kcal / mol和5.9×10-12M。计算机模拟的免疫反应显示出丰富的免疫球蛋白，增加的干扰素-γ产生和巨噬细胞活化，这对于针对溃疡分枝杆菌的免疫反应至关重要。此外，还进行了二硫键桥接和计算机克隆。这些结果表明，如果通过实验验证，该疫苗将是抗溃疡分枝杆菌并预防布鲁氏溃疡病的有前途的候选药物。进行同源建模。分子对接和动力学模拟揭示了疫苗与收费型受体2之间的强而稳定的相互作用。结合能和解离常数分别为-15.3 kcal / mol和5.9×10-12M。计算机模拟的免疫反应显示出丰富的免疫球蛋白，增加的干扰素-γ产生和巨噬细胞活化，这对于针对溃疡分枝杆菌的免疫反应至关重要。此外，还进行了二硫键桥接和计算机克隆。这些结果表明，如果通过实验验证，该疫苗将是抗溃疡分枝杆菌并预防布鲁氏溃疡病的有前途的候选药物。结合能和解离常数分别为-15.3 kcal / mol和5.9×10-12M。计算机模拟的免疫反应显示出丰富的免疫球蛋白，增加的干扰素-γ产生和巨噬细胞活化，这对于针对溃疡分枝杆菌的免疫反应至关重要。此外，还进行了二硫键桥接和计算机克隆。这些结果表明，如果通过实验验证，该疫苗将是抗溃疡分枝杆菌并预防布鲁氏溃疡病的有前途的候选药物。结合能和解离常数分别为-15.3 kcal / mol和5.9×10-12M。计算机模拟的免疫反应显示出丰富的免疫球蛋白，增加的干扰素-γ产生和巨噬细胞活化，这对于针对溃疡分枝杆菌的免疫反应至关重要。此外，还进行了二硫键桥接和计算机克隆。这些结果表明，如果通过实验验证，该疫苗将是抗溃疡分枝杆菌并预防布鲁氏溃疡病的有前途的候选药物。