■猪流行性腹泻(PED),由猪流行性腹泻病毒(PEDV)引起,与高死亡率和高发病率有关,尤其是新生猪。这给养猪业造成了巨大的经济损失。发现基于PEDV基因型II的疫苗可针对异源和同源挑战提供更好的免疫力;特别是,刺突(S)蛋白,已知在感染过程中发挥重要作用,是疫苗开发的理想选择。
■本研究旨在使用免疫信息学方法设计一种靶向PEDVGIIa毒株S蛋白的多表位亚单位疫苗。
■使用各种生物信息学工具来预测HTL,CTL,和B细胞表位。使用合适的接头连接表位并与CTB佐剂和M-配体缀合。然后将最终的多表位疫苗构建体(fMEVc)对接至toll样受体4(TLR4)。然后使用GROMACS模拟fMEVc-TLR4复合物的稳定性。然后使用C-immsim来预测fMEVc的体外免疫应答。
■预测六个表位诱导抗体产生,预测十个表位诱导CTL反应,预测四个表位诱导HTL应答。与CTB佐剂和M-配体缀合的组装表位,fMEVc,是抗原性的,非过敏性,稳定,和可溶性。该构建体显示出对TLR4有利的结合亲和力,并且通过分子动力学模拟显示该蛋白质复合物是稳定的。免疫后诱导了强烈的免疫反应,通过免疫刺激证明。
■总而言之,本研究中设计的PEDV多表位亚单位疫苗构建体显示出有希望的抗原性,稳定性,和免疫原性,引发强大的免疫反应,并表明其作为进一步疫苗开发的候选者的潜力。
UNASSIGNED: Porcine epidemic diarrhea (PED), caused by the porcine epidemic diarrhea virus (PEDV), is associated with high mortality and morbidity rates, especially in neonatal pigs. This has resulted in significant economic losses for the pig industry. PEDV genotype II-based vaccines were found to confer better immunity against both heterologous and homologous challenges; specifically, spike (S) proteins, which are known to play a significant role during infection, are ideal for vaccine development.
UNASSIGNED: This study aims to design a multi-epitope subunit vaccine targeting the S protein of the PEDV GIIa strain using an immunoinformatics approach.
UNASSIGNED: Various bioinformatics tools were used to predict HTL, CTL, and B-cell epitopes. The epitopes were connected using appropriate linkers and conjugated with the CTB adjuvant and M-ligand. The final multiepitope vaccine construct (fMEVc) was then docked to toll-like receptor 4 (TLR4). The stability of the fMEVc-TLR4 complex was then simulated using GROMACS. C-immsim was then used to predict the in vitro immune response of the fMEVc.
UNASSIGNED: Six epitopes were predicted to induce antibody production, ten epitopes were predicted to induce CTL responses, and four epitopes were predicted to induce HTL responses. The assembled epitopes conjugated with the CTB adjuvant and M-ligand, fMEVc, is antigenic, non-allergenic, stable, and soluble. The construct showed a favorable binding affinity for TLR4, and the protein complex was shown to be stable through molecular dynamics simulations. A robust immune response was induced after immunization, as demonstrated through immune stimulation.
UNASSIGNED: In conclusion, the multi-epitope subunit vaccine construct for PEDV designed in this study exhibits promising antigenicity, stability, and immunogenicity, eliciting robust immune responses and suggesting its potential as a candidate for further vaccine development.