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

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-02-26 DOI:10.1007/s10529-023-03464-x

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.

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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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