Proteomics-based vaccine targets annotation and design of subunit and mRNA-based vaccines for Monkeypox virus (MPXV) against the recent outbreak

• Published in: Computers in biology and medicine Vol. 159; p. 106893
• Main Authors: Jin, Yifan, Fayyaz, Addeela, Liaqat, Ayesha, Khan, Abbas, Alshammari, Abdulrahman, Wang, Yanjing, Gu, Ruo-Xu, Wei, Dong-Qing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.06.2023; Elsevier Limited; Published by Elsevier Ltd
• Subjects: Annotations; Antigen presentation; Antigens; Cloning; Computational Biology - methods; Cytokines; Cytotoxicity; Dendritic cells; Design; Disease Outbreaks; E coli; Epidemics; Epitopes; Epitopes, B-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - chemistry; Escherichia coli; Free energy; Health risks; Immune response; Immune simulation; Immune system; Immunoglobulin G; Immunoglobulin M; Interleukins; Lymphocytes; Lymphocytes T; Molecular docking; Molecular Docking Simulation; Monkeypox; Monkeypox virus; mRNA; mRNA vaccines; Multi-epitopes; Pathogens; Peptides; Proteins; Proteomes; Proteomics; Public health; Smallpox; TLR2 protein; Toll-like receptors; Vaccines; Viral infections; Viral Vaccines - genetics; Viruses; γ-Interferon; mRNA; Vaccines; Immune simulation; Multi-epitopes; Monkeypox
• ISSN: 0010-4825; 1879-0534; 1879-0534
• DOI: 10.1016/j.compbiomed.2023.106893

Monkeypox Virus (MPXV) is a growing public health threat with increasing cases and fatalities globally. To date, no specific vaccine or small molecule therapeutic choices are available for the treatment of MPXV disease. In this work, we employed proteomics and structural vaccinology approaches to design mRNA and multi-epitopes-based vaccines (MVC) against MPXV. We first identified ten proteins from the whole proteome of MPXV as potential vaccine targets. We then employed structural vaccinology approaches to map potential epitopes of these proteins for B cell, cytotoxic T lymphocytes (CTL), and Helper T lymphocytes (HTL). Finally, 9 CTL, 6 B cell, and 5 HTL epitopes were joined together through suitable linkers to construct MVC (multi-epitope vaccine) and mRNA-based vaccines. Molecular docking, binding free energy calculation, and in silico cloning revealed robust interaction of the designed MVC with toll-like receptor 2 (TLR2) and efficient expression in E. Coli K12 strain. The immune simulation results revealed that the antigen titer after the injection reached to the maximum level on the 5th day and an abrupt decline in the antigen titer was observed upon the production of IgM, IgG and IgM + IgG, dendritic cells, IFN-gamma, and IL (interleukins), which suggested the potential of our designed vaccine candidate for inducing an immune response against MPXV. [Display omitted] •Monkeypox Virus (MPXV) is a growing public health threat with growing cases and fatalities globally.•To design mRNA and multi-epitopes based vaccines against MPXV, we employed immunoinformatics approaches.•Our results revealed ten proteins as potential vaccine targets from the whole proteome.•Furthermore, 9 CTL, 6 B cell, and 5 HTL epitopes were joined together to construct MVC and mRNA-based vaccines.•Docking, in silico cloning and immune simulation validated our vaccine construct and demands a prompt experimental testing.