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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Acknowledgements
Fatemeh Heidarnejad was supported by Pasteur Institute of Iran, Tehran, Iran to pursue her study in the Ph.D. thesis.
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FH: Conceptualization, Methodology, Software, Formal analysis, Writing-original draft, Writing-review & editing, Visualization; AN: Methodology, Software, Formal analysis, Writing-review & editing; SMS: Formal analysis, Writing-review & editing; PMP: Formal analysis, Writing-review & editing; FR: Methodology, Writing-review & editing; HN: Software, Writing-review & editing; SA: Formal analysis, Writing-review & editing; AB: Conceptualization, Methodology, Formal analysis, Writing-original draft, Writing-review & editing, Supervision, Project administration.
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Heidarnejad, F., Namvar, A., Sadat, S.M. et al. In silico designing of novel epitope-based peptide vaccines against HIV-1. Biotechnol Lett 46, 315–354 (2024). https://doi.org/10.1007/s10529-023-03464-x
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DOI: https://doi.org/10.1007/s10529-023-03464-x