In silico designing of novel epitope-based peptide vaccines against HIV-1

IF 2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Fatemeh Heidarnejad, Ali Namvar, Seyed Mehdi Sadat, Parisa Moradi Pordanjani, Fatemeh Rezaei, Haideh Namdari, Sina Arjmand, Azam Bolhassani
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Abstract

The HIV-1 virus has been regarded as a catastrophe for human well-being. The global incidence of HIV-1-infected individuals is increasing. Hence, development of effective immunostimulatory molecules has recently attracted an increasing attention in the field of vaccine design against HIV-1 infection. In this study, we explored the impacts of CD40L and IFN-γ as immunostimulatory adjuvants for our candidate HIV-1 Nef vaccine in human and mouse using immunoinformatics analyses. Overall, 18 IFN-γ-based vaccine constructs (9 constructs in human and 9 constructs in mouse), and 18 CD40L-based vaccine constructs (9 constructs in human and 9 constructs in mouse) were designed. To find immunogenic epitopes, important characteristics of each component (e.g., MHC-I and MHC-II binding, and peptide-MHC-I/MHC-II molecular docking) were determined. Then, the selected epitopes were applied to create multiepitope constructs. Finally, the physicochemical properties, linear and discontinuous B cell epitopes, and molecular interaction between the 3D structure of each construct and CD40, IFN-γ receptor or toll-like receptors (TLRs) were predicted. Our data showed that the full-length CD40L and IFN-γ linked to the N-terminal region of Nef were capable of inducing more effective immune response than multiepitope vaccine constructs. Moreover, molecular docking of the non-allergenic full-length- and epitope-based CD40L and IFN-γ constructs to their cognate receptors, CD40 and IFN-γ receptors, and TLRs 4 and 5 in mouse were more potent than in human. Generally, these findings suggest that the full forms of these adjuvants could be more efficient for improvement of HIV-1 Nef vaccine candidate compared to the designed multiepitope-based constructs.

Graphical abstract

Abstract Image

基于表位的新型多肽疫苗预防 HIV-1 的硅学设计
摘要 HIV-1 病毒被视为人类福祉的灾难。全球 HIV-1 感染者的发病率不断上升。因此,开发有效的免疫刺激分子最近在针对 HIV-1 感染的疫苗设计领域引起了越来越多的关注。在本研究中,我们利用免疫信息学分析探讨了 CD40L 和 IFN-γ 作为候选 HIV-1 Nef 疫苗免疫刺激佐剂对人类和小鼠的影响。总共设计了 18 种基于 IFN-γ 的疫苗构建物(9 种构建物用于人,9 种构建物用于小鼠)和 18 种基于 CD40L 的疫苗构建物(9 种构建物用于人,9 种构建物用于小鼠)。为了找到免疫原表位,确定了每个成分的重要特征(如与 MHC-I 和 MHC-II 的结合以及肽-MHC-I/MHC-II 的分子对接)。然后,将选定的表位用于创建多表位构建体。最后,预测了每种构建物的理化性质、线性和非连续 B 细胞表位,以及三维结构与 CD40、IFN-γ 受体或类毒素受体(TLR)之间的分子相互作用。我们的数据显示,与多表位疫苗构建物相比,与 Nef N 端区域相连的全长 CD40L 和 IFN-γ 能够诱导更有效的免疫反应。此外,在小鼠体内,非过敏性全长和基于表位的 CD40L 和 IFN-γ 构建物与它们的同源受体、CD40 和 IFN-γ 受体以及 TLRs 4 和 5 的分子对接比在人体内更有效。总体而言,这些研究结果表明,与设计的基于多表位的构建物相比,这些佐剂的完整形式可以更有效地改进 HIV-1 Nef 候选疫苗。
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来源期刊
Biotechnology Letters
Biotechnology Letters 工程技术-生物工程与应用微生物
CiteScore
5.90
自引率
3.70%
发文量
108
审稿时长
1.2 months
期刊介绍: Biotechnology Letters is the world’s leading rapid-publication primary journal dedicated to biotechnology as a whole – that is to topics relating to actual or potential applications of biological reactions affected by microbial, plant or animal cells and biocatalysts derived from them. All relevant aspects of molecular biology, genetics and cell biochemistry, of process and reactor design, of pre- and post-treatment steps, and of manufacturing or service operations are therefore included. Contributions from industrial and academic laboratories are equally welcome. We also welcome contributions covering biotechnological aspects of regenerative medicine and biomaterials and also cancer biotechnology. Criteria for the acceptance of papers relate to our aim of publishing useful and informative results that will be of value to other workers in related fields. The emphasis is very much on novelty and immediacy in order to justify rapid publication of authors’ results. It should be noted, however, that we do not normally publish papers (but this is not absolute) that deal with unidentified consortia of microorganisms (e.g. as in activated sludge) as these results may not be easily reproducible in other laboratories. Papers describing the isolation and identification of microorganisms are not regarded as appropriate but such information can be appended as supporting information to a paper. Papers dealing with simple process development are usually considered to lack sufficient novelty or interest to warrant publication.
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