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

• Published in: Biotechnology letters 2024-06, Vol.46 (3), p.315-354
• Main Authors: Heidarnejad, Fatemeh, Namvar, Ali, Sadat, Seyed Mehdi, Pordanjani, Parisa Moradi, Rezaei, Fatemeh, Namdari, Haideh, Arjmand, Sina, Bolhassani, Azam
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - pharmacology; AIDS Vaccines - chemistry; AIDS Vaccines - immunology; Animals; Applied Microbiology; Biochemistry; Biomedical and Life Sciences; Biotechnology; CD40 antigen; CD40 Ligand - chemistry; CD40 Ligand - immunology; CD40L protein; Computer Simulation; Epitopes; Epitopes - chemistry; Epitopes - immunology; Epitopes, B-Lymphocyte - chemistry; Epitopes, B-Lymphocyte - immunology; HIV; HIV Infections - immunology; HIV Infections - prevention & control; HIV-1; Human immunodeficiency virus; Humans; Immune response; Immune system; Immunogenicity; Immunostimulation; Interferon-gamma - immunology; Interferon-gamma - metabolism; Life Sciences; Major histocompatibility complex; Mice; Microbiology; Molecular docking; Molecular Docking Simulation; Molecular interactions; Molecular structure; nef Gene Products, Human Immunodeficiency Virus - chemistry; nef Gene Products, Human Immunodeficiency Virus - immunology; Original Research Paper; Peptides; Physicochemical properties; Protein Subunit Vaccines - chemistry; Protein Subunit Vaccines - immunology; Toll-like receptors; Vaccines; Well being; γ-Interferon
• ISSN: 0141-5492; 1573-6776; 1573-6776
• DOI: 10.1007/s10529-023-03464-x

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