整合免疫与生物信息学辅助设计的抗HIV感染新型表位疫苗：一项基于全基因组的研究

Integrated Immuno and bioinformatics assisted novel epitope vaccine against HIV infection: a study based on complete genome.

作者信息

Mishra Saurav Kumar, Guendouzi Abdelkrim, Kumar Neeraj, Sharma Ganesh, Alqahtani Taha, Zaki Magdi E A, Al Mashud Md Abdullah, Tiruneh Yewulsew Kebede, Georrge John J

机构信息

Department of Bioinformatics, University of North Bengal, District-Darjeeling, West Bengal, 734013, India.

Laboratory of Chemistry: Synthesis, Properties and Application, Faculty of Sciences and Technology, University of Saida, Saïda, Algeria.

出版信息

Virol J. 2025 Jul 9;22(1):228. doi: 10.1186/s12985-025-02764-0.

DOI:10.1186/s12985-025-02764-0

PMID:40634976

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12239378/

Abstract

BACKGROUND

As the HIV-based complication is still going on with the high infection and mortality rate, it requires a novel strategy to combat this infection due to the unavailability of proper therapeutic. Therefore, we utilize integrated immuno and bioinformatics approaches in this study to design a peptide vaccine against HIV infection by targeting its complete genome.

METHODS

The complete genome sequence was analyzed, and the potential B and T cells were predicted. Among the predicted epitopes, the promising ones were selected and further used with the adjuvant and linker to formulate a vaccine candidate. The vaccine was modeled, and its activity and stability towards the TLRs were analyzed via docking and dynamics (500ns). The vaccine-generated immune activity and expression via - cloning were also evaluated.

RESULTS

A total of 6 B cells, 7 CTL, and 6 HTL were identified as an immunodominant epitope and used for vaccine formulation. These epitopes were fused together via linkers, and their efficiency and constancy were enhanced with Adjuvant, PADRE epitope, and His-tag. Further, the formulated vaccine shows high population coverage and stable features based on the 2D and 3D assessments. The docking investigation demonstrated the strong activity of the vaccine towards the TLR2 and TLR3, having binding affinity − 10.8 kcal/mol-1 and − 15.8 kcal/mol-1, and also disclosed remarkable constancy based on the 500ns simulation period. The vaccine-assisted immune simulation and expression level in the vector revealed a robust immune response towards the host based on the vaccination and a significant expression level.

CONCLUSIONS

Based on the integrated approach and validation steps, the overall finding suggests that the formulated vaccine may have strongly immunodominant properties and could combat the infection.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s12985-025-02764-0.

摘要

背景

由于基于HIV的并发症仍在以高感染率和死亡率持续存在，鉴于缺乏合适的治疗方法，需要一种新的策略来对抗这种感染。因此，在本研究中，我们利用综合免疫和生物信息学方法，通过靶向HIV全基因组来设计一种抗HIV感染的肽疫苗。

方法

分析全基因组序列，并预测潜在的B细胞和T细胞。在预测的表位中，选择有前景的表位，并进一步与佐剂和连接子一起用于制备候选疫苗。对疫苗进行建模，并通过对接和动力学分析（500纳秒）评估其对Toll样受体（TLR）的活性和稳定性。还评估了疫苗产生的免疫活性和通过克隆的表达。

结果

共鉴定出6个B细胞表位、7个细胞毒性T淋巴细胞（CTL）表位和6个辅助性T淋巴细胞（HTL）表位作为免疫显性表位，并用于疫苗制备。这些表位通过连接子融合在一起，佐剂、PADRE表位和组氨酸标签增强了它们的效率和稳定性。此外，根据二维和三维评估，制备的疫苗显示出高群体覆盖率和稳定的特性。对接研究表明，该疫苗对TLR2和TLR3具有很强的活性，结合亲和力分别为−10.8千卡/摩尔和−15.8千卡/摩尔，并且在500纳秒的模拟期内也显示出显著的稳定性。疫苗辅助的免疫模拟和载体中的表达水平显示，基于疫苗接种对宿主有强烈的免疫反应和显著的表达水平。