In-silico design of a multivalent epitope-based vaccine against Candida auris
In-silico design of a multivalent epitope-based vaccine against Candida auris
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DOI：
10.1016/j.micpath.2021.104879
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发表时间：
2021-04-18
影响因子：
3.8
通讯作者：
Amin-ul Mannan, M.
中科院分区：
文献类型：
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作者：
Akhtar, Nahid;Joshi, Amit;Amin-ul Mannan, M.
耳念珠菌是一种迅速出现的致病性高的人类致病菌。最近的报告表明，新的临床分离株对主要类别的抗真菌药物表现出耐药性。由于耐药的出现，寻求治疗金黄色葡萄球菌的新疗法势在必行。这种强效疫苗可能是对付顽固性和多重耐药病原体的一种有希望的策略。利用芯片技术，我们设计了一种新的抗金黄色葡萄球菌多价疫苗。我们选择了凝集素样序列-3 (Als3)，一种与毒力有关的粘附蛋白。以金黄色葡萄球菌的Als3p蛋白为靶点预测T细胞和B细胞表位。选择无毒、非致敏、高度保守、抗原性强、能诱导干扰素合成的抗原表位进行疫苗设计。选择的抗原表位与合适的佐剂连接，构建最终的疫苗。预计该疫苗结构稳定、可溶、抗原性强、不过敏，具有理想的物理化学性质。我们还构建了疫苗的3D模型，并用Ramachandran图进行验证。通过分子对接实验确定疫苗结构与toll样受体（TLR）和主要组织相容性复合体（MHC）相互作用的能力。通过分子动力学模拟发现，该疫苗构建体与TLR和MHC的结合能稳定。此外，硅克隆分析表明，该疫苗结构可以成功克隆并在大肠杆菌中表达。基于这些结果，我们推测我们的候选疫苗可以作为治疗金黄色葡萄球菌的替代疗法。然而，疫苗模型的有效性和安全性需要通过进行体内研究来确定。
Candida auris is a rapidly emerging human pathogenic fungus with a high mortality rate. Recent report suggests that the new clinical isolates are showing resistance to the major classes of antifungal drugs. Due to the emergence of drug resistance, it becomes imperative to seek novel therapies for the treatment of C. auris. The potent vaccine could be one of the promising strategies for recalcitrant and multidrug-resistant pathogens. Using in silico approach we designed a novel multivalent vaccine against C. auris. We have selected the agglutinin-like sequence-3 (Als3) an adhesion protein, involved in virulence. The Als3p protein of C. auris was targeted to predict T cell and B cell epitopes. Epitopes which were found to be non-toxic, non-allergenic, highly conserved, and antigenic and could induce interferon-gamma synthesis were selected for vaccine design. The selected epitopes were linked with suitable adjuvants to construct the final vaccine. The vaccine construct was predicted to be stable, soluble, antigenic, non-allergic with desirable physicochemical properties. We also constructed the 3D model of the vaccine and validated it with the Ramachandran plot. The ability of the vaccine construct to interact with Toll-like receptor (TLR) and major histocompatibility complex (MHC) was determined by molecular docking experiments. The binding energy of the vaccine construct with the TLR and MHC were found to be stable as predicted by molecular dynamics simulation. Further, in-silico cloning analysis showed that the vaccine construct can be successfully cloned and expressed in E. coli. Based on the results, we surmise that our candidate vaccine can be used as an alternative therapy for the treatment of C. auris. However, the efficacy and the safety of the vaccine model need to be determined by performing in vivo studies.