Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, Ajmer 305817, Rajasthan, India.
Department of Environmental Biotechnology, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India.
Vaccine. 2018 Apr 19;36(17):2262-2272. doi: 10.1016/j.vaccine.2018.03.042. Epub 2018 Mar 20.
The end goal of HIV vaccine designing requires novel strategies to elicit a strong humoral and cell-mediated immune response. The emergence of drug resistance and the requirement of next line treatment necessitate the finding of the potential and immunogenic vaccine candidate. This study employed a novel immunoinformatics approach to design multi-epitope subunit vaccine against HIV infection. Here, we designed the subunit vaccine by the combination of CTL, HTL and BCL epitopes along with suitable adjuvant and linkers. Physiochemical characterization of subunit vaccine was assessed to ensure its thermostability, theoretical PI, and amphipathic behavior. In further assessment, subunit vaccine was found to be immunogenic with the capability to generate humoral and cell-mediated immune response. Further, homology modeling and refinement was performed and the refined modeled structure was used for molecular docking with the immune receptor (TLR-3) present on lymphocyte cells. Consequently, molecular dynamics simulation ensured the molecular interaction between TLR-3 and subunit vaccine candidate. Disulfide engineering was performed by placing the cysteine residues in the region of high mobility to enhance the vaccine stability. At last, in silico cloning was performed to warrant the translational efficiency and microbial expression of the designed vaccine.
HIV 疫苗设计的最终目标需要新的策略来引发强烈的体液和细胞介导的免疫反应。耐药性的出现和下一线治疗的需求需要寻找有潜力和免疫原性的疫苗候选物。本研究采用新的免疫信息学方法设计针对 HIV 感染的多表位亚单位疫苗。在这里，我们通过结合 CTL、HTL 和 BCL 表位以及合适的佐剂和接头来设计亚单位疫苗。对亚单位疫苗的理化特性进行了评估，以确保其热稳定性、理论等电点和两亲性。在进一步的评估中，发现亚单位疫苗具有免疫原性，能够产生体液和细胞介导的免疫反应。此外，还进行了同源建模和细化，并将细化的模型结构用于与淋巴细胞上存在的免疫受体（TLR-3）的分子对接。随后，分子动力学模拟确保了 TLR-3 和亚单位疫苗候选物之间的分子相互作用。通过将半胱氨酸残基放置在高迁移率区域来进行二硫键工程，以提高疫苗的稳定性。最后，进行了计算机克隆，以保证设计疫苗的翻译效率和微生物表达。
