Identification of novel T-cell epitopes on monkeypox virus and development of multi-epitopes vaccine using immunoinformatics approaches

• Published in: Journal of biomolecular structure & dynamics 2024-07, Vol.42 (10), p.5349-5364
• Main Authors: Ezzemani, Wahiba, Ouladlahsen, Ahd, Altawalah, Haya, Saile, Rachid, Sarih, M'hammed, Kettani, Anass, Ezzikouri, Sayeh
• Format: Article
• Language: English
• Subjects: Computational Biology - methods; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Humans; Immunoinformatics; in-silico; Molecular Docking Simulation; Molecular Dynamics Simulation; Monkeypox virus; Monkeypox virus - immunology; Mpox (monkeypox); multi-epitopes vaccine; Protein Binding; smallpox vaccine; Smallpox Vaccine - immunology; TLR9; Toll-Like Receptor 9 - chemistry; Toll-Like Receptor 9 - immunology; Vaccines, Subunit - chemistry; Vaccines, Subunit - immunology
• ISSN: 0739-1102; 1538-0254; 1538-0254
• DOI: 10.1080/07391102.2023.2226733

Monkeypox virus (MPV) is closely related to the smallpox virus, and previous data from Africa suggest that the smallpox vaccine (VARV) is at least 85% effective in preventing MPV. No multi-epitope vaccine has yet been developed to prevent MPV infection. In this work, we used in silico structural biology and advanced immunoinformatic strategies to design a multi-epitope subunit vaccine against MPV infection. The designed vaccine sequence is adjuvanted with CpG-ODN and includes HTL/CTL epitopes for similar proteins between vaccinia virus (VACV) that induced T-cell production in vaccinated volunteers and the first draft sequence of the MPV genome associated with the suspected outbreak in several countries, May 2022. In addition, the specific binding of the modified vaccine and the immune Toll-like receptor 9 (TLR9) was estimated by molecular interaction studies. Strong interaction in the binding groove as well as good docking scores confirmed the stringency of the modified vaccine. The stability of the interaction was confirmed by a classical molecular dynamics simulation and normal mode analysis. Then, the immune simulation also indicated the ability of this vaccine to induce an effective immune response against MPV. Codon optimization and in silico cloning of the vaccine into the pET-28a (+) vector also showed its expression potential in the E. coli K12 system. The promising data obtained from the various in silico studies indicate that this vaccine is effective against MPV. However, additional in vitro and in vivo studies are still needed to confirm its efficacy. Communicated by Ramaswamy H. Sarma