瞄准 HIV-1 保守区:亚洲疫苗创新的免疫形式化途径。

IF 2.6 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
PLoS ONE Pub Date : 2025-03-21 eCollection Date: 2025-01-01 DOI:10.1371/journal.pone.0317382
Akmal Zubair, Ahmed Al-Emam, Muhammad Ali, Syeda Maryam Hussain, Ranya Mohammed Elmagzoub
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引用次数: 0

摘要

体液和细胞介导的免疫系统刺激的结合对于开发有效的HIV疫苗至关重要。传统的治疗方案和耐药性带来的挑战需要发现一种能够引起强烈免疫反应的可行的候选疫苗。本研究旨在利用独特的免疫信息学方法开发具有多表位成分的HIV疫苗。亚单位疫苗包括b细胞、辅助性t细胞和细胞毒性t细胞表位,以及适当的佐剂和连接体,用于鉴定Pol、Vpr、Gag、Tat、Env、Nef和Vif蛋白中的保守区域。HIV亚单位疫苗显示出激活细胞介导和体液免疫反应的潜力,表明其免疫原性。同源建模和精化的应用进一步提高了模型的精度。随后,分子对接程序利用改进的模型结构与淋巴细胞中的免疫受体TLR-3结合。随后,利用分子动力学模型研究了亚单位疫苗与TLR-3的潜在相互作用。通过将半胱氨酸残基插入高度灵活的区域,细致的二硫工程技术提高了疫苗的稳定性。最后,采用硅克隆来验证在微生物环境下翻译和生产疫苗的有效性。该疫苗在人口覆盖率方面显示出令人鼓舞的结果,达到全球人口的82%,在亚洲具有非凡的效力,覆盖了高达95%的人口。我们的HIV候选疫苗是高度稳定的,并引起对HIV-1的强大免疫反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting HIV-1 conserved regions: An immunoinformatic pathway to vaccine innovation for the Asia.

A combination of humoral and cell-mediated immune system stimulation is essential for developing an effective HIV vaccine. Traditional treatment options and the challenges posed by drug resistance necessitate the discovery of a viable vaccine candidate capable of eliciting a robust immunological response. This research aims to develop an HIV vaccine with a multi-epitope component using a unique immunoinformatics approach. A subunit vaccine comprising B-cell, helper T-cell, and cytotoxic T-cell epitopes, along with appropriate adjuvants and linkers, was employed to identify conserved regions in the Pol, Vpr, Gag, Tat, Env, Nef, and Vif proteins. The HIV subunit vaccine demonstrated the potential to activate both cell-mediated and humoral immune responses, indicating its immunogenicity. The application of homology modeling and refinement further enhanced the model's accuracy. Subsequently, the molecular docking procedure utilized the refined model structure to bind to the immunological receptor TLR-3 in lymphocyte cells. Following this, the potential interactions of the subunit vaccine with TLR-3 were investigated using molecular dynamics modeling. The vaccine's stability was improved through a meticulous disulfide engineering technique that involved inserting cysteine residues into highly flexible regions. Finally, in silico cloning was employed to validate the efficacy of translating and producing the vaccine in a microbiological setting. The vaccine shows promising results in terms of population coverage, reaching 82% of the global population, with extraordinary efficacy in Asia, covering up to 95% of the population. Our HIV vaccine candidate is highly stable and elicits a robust immune response against HIV-1.

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来源期刊
PLoS ONE
PLoS ONE 生物-生物学
CiteScore
6.20
自引率
5.40%
发文量
14242
审稿时长
3.7 months
期刊介绍: PLOS ONE is an international, peer-reviewed, open-access, online publication. PLOS ONE welcomes reports on primary research from any scientific discipline. It provides: * Open-access—freely accessible online, authors retain copyright * Fast publication times * Peer review by expert, practicing researchers * Post-publication tools to indicate quality and impact * Community-based dialogue on articles * Worldwide media coverage
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