A therapeutic epitopes-based vaccine engineering against <i>Salmonella enterica</i> XDR strains for typhoid fever: a Pan-vaccinomics approach
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A prevalent food-borne pathogen, <i>Salmonella enterica serotypes Typhi,</i> is responsible for gastrointestinal and systemic infections globally. <i>Salmonella</i> vaccines are the most effective, however, producing a broad-spectrum vaccine remains challenging due to <i>Salmonella’s</i> many serotypes. Efforts are urgently required to develop a novel vaccine candidate that can tackle all <i>S. Typhi</i> strains because of their high resistance to multiple kinds of antibiotics (particularly the XDR H58 strain). In this work, we used a computational pangenome-based vaccine design technique on all available (<i>n</i> = 119) <i>S. Typhi</i> reference genomes and identified one TonB-dependent siderophore receptor (WP_001034967.1) as highly conserved and prospective vaccine candidates from the predicted core genome (<i>n</i> = 3,351). The applied pan-proteomics and Immunoinformatic approaches help in the identification of four epitopes that may trigger adequate host body immune responses. Furthermore, the proposed vaccine ensemble demonstrates a stable binding conformation with the examined immunological receptor (HLAs and TRL2/4) and has large interaction energy determined <i>via</i> molecular docking and molecular dynamics simulation techniques. Eventually, an expression vector for the <i>Escherichia. coli</i> K12 strain was constructed from the vaccine sequence. Additional analysis revealed that the vaccine may help to elicit strong immune responses for typhoid infections, however, experimental analysis is required to verify the vaccine’s effectiveness based on these results. Moreover, the applied computer-assisted vaccine design may considerably decrease vaccine development costs and speed up the process. The study’s findings are intriguing, but they must be evaluated in the experimental labs to confirm the developed vaccine’s biological efficiency against XDR <i>S. Typhi</i>. Communicated by Ramaswamy H. Sarma
作为一种常见食源性致病菌，伤寒沙门氏菌（Salmonella enterica serotype Typhi）在全球范围内引发胃肠道与全身性感染。沙门氏菌（Salmonella）疫苗是防控该菌感染的最有效手段，但由于沙门氏菌血清型繁多，研发广谱疫苗仍面临诸多挑战。鉴于伤寒沙门氏菌对多种抗生素具有高度耐药性（尤其是广泛耐药[Extensively Drug Resistant, XDR]的H58型菌株），迫切需要开发能够覆盖所有伤寒沙门氏菌菌株的新型候选疫苗。本研究针对所有可用的119株伤寒沙门氏菌参考基因组（*n*=119），采用基于泛基因组（pangenome）的计算疫苗设计方法，从预测得到的3351个核心基因（*n*=3351）中筛选出1个高度保守且具有开发潜力的TonB依赖性铁载体受体（TonB-dependent siderophore receptor，WP_001034967.1）作为候选疫苗靶点。本研究采用的泛蛋白质组学（pan-proteomics）与免疫信息学（immunoinformatics）方法，成功筛选出4个可有效触发宿主免疫应答的表位（epitopes）。此外，通过分子对接（molecular docking）与分子动力学模拟（molecular dynamics simulation）技术验证发现，所设计的多表位疫苗与所检测的免疫受体（人类白细胞抗原[Human Leukocyte Antigens, HLAs]及Toll样受体2/4[TLR2/4]，原文笔误为TRL2/4）可形成稳定的结合构象，且具有较强的相互作用能。最终，基于该疫苗序列成功构建了适用于大肠杆菌（Escherichia coli）K12菌株的表达载体。额外分析表明，该疫苗有望引发针对伤寒感染的强效免疫应答，但仍需通过实验验证本研究结果中疫苗的实际防控效果。此外，本研究采用的计算机辅助疫苗设计策略可显著降低疫苗研发成本并缩短研发周期。本研究的发现颇具研究价值，但仍需在实验室开展实验验证，以确认所开发疫苗对广泛耐药伤寒沙门氏菌的生物学功效。本文由Ramaswamy H. Sarma供稿。
