PDF(Pubmed)
Abstract：
Aeromonas hydrophila, a gram-negative coccobacillus bacterium, can cause various infections in humans, including septic arthritis, diarrhea (traveler\'s diarrhea), gastroenteritis, skin and wound infections, meningitis, fulminating septicemia, enterocolitis, peritonitis, and endocarditis. It frequently occurs in aquatic environments and readily contacts humans, leading to high infection rates. This bacterium has exhibited resistance to numerous commercial antibiotics, and no vaccine has yet been developed. Aiming to combat the alarmingly high infection rate, this study utilizes in silico techniques to design a multi-epitope vaccine (MEV) candidate against this bacterium based on its aerolysin toxin, which is the most toxic and highly conserved virulence factor among the Aeromonas species. After retrieval, aerolysin was processed for B-cell and T-cell epitope mapping. Once filtered for toxicity, antigenicity, allergenicity, and solubility, the chosen epitopes were combined with an adjuvant and specific linkers to create a vaccine construct. These linkers and the adjuvant enhance the MEV\'s ability to elicit robust immune responses. Analyses of the predicted and improved vaccine structure revealed that 75.5%, 19.8%, and 1.3% of its amino acids occupy the most favored, additional allowed, and generously allowed regions, respectively, while its ERRAT score reached nearly 70%. Docking simulations showed the MEV exhibiting the highest interaction and binding energies (-1,023.4 kcal/mol, -923.2 kcal/mol, and -988.3 kcal/mol) with TLR-4, MHC-I, and MHC-II receptors. Further molecular dynamics simulations demonstrated the docked complexes\' remarkable stability and maximum interactions, i.e., uniform RMSD, fluctuated RMSF, and lowest binding net energy. In silico models also predict the vaccine will stimulate a variety of immunological pathways following administration. These analyses suggest the vaccine\'s efficacy in inducing robust immune responses against A. hydrophila. With high solubility and no predicted allergic responses or toxicity, it appears safe for administration in both healthy and A. hydrophila-infected individuals.
摘要：
嗜水气单胞菌,革兰氏阴性球杆菌,会导致人类的各种感染，包括化脓性关节炎,腹泻（旅行者腹泻），胃肠炎,皮肤和伤口感染，脑膜炎,暴发性败血病，小肠结肠炎,腹膜炎,和心内膜炎.它经常发生在水生环境中，并且容易与人类接触，导致高感染率。这种细菌对许多商业抗生素表现出抗性，目前还没有研制出疫苗。为了对抗惊人的高感染率，这项研究利用计算机技术设计了一种多表位疫苗（MEV）候选基于该细菌的气溶素毒素，是气单胞菌中毒性最强、高度保守的毒力因子。检索后,对空气溶素进行处理以进行B细胞和T细胞表位作图。一旦过滤毒性，抗原性,变应原性,和溶解度，将选择的表位与佐剂和特异性接头组合以创建疫苗构建体。这些接头和佐剂增强了MEV引发强烈免疫应答的能力。对预测和改进的疫苗结构的分析表明，75.5%，19.8%,1.3%的氨基酸占据了最受欢迎的位置，额外允许，慷慨允许的地区，分别,而其ERRAT评分达到近70%。对接模拟显示，MEV表现出最高的相互作用和结合能（-1,023.4kcal/mol，-923.2千卡/摩尔，和-988.3kcal/mol）与TLR-4，MHC-I，和MHC-II受体。进一步的分子动力学模拟证明了对接复合物的显着稳定性和最大的相互作用，即，统一的RMSD，波动的RMSF，和最低的结合净能量。计算机模拟模型还预测疫苗在施用后将刺激多种免疫途径。这些分析表明该疫苗在诱导针对嗜水气单胞菌的强烈免疫应答方面的功效。溶解度高，没有预测的过敏反应或毒性，在健康个体和嗜水菌感染个体中给药都是安全的。
