In-silico formulation of a next-generation polyvalent vaccine against multiple strains of monkeypox virus and other related poxviruses

• Published in: PloS one Vol. 19; no. 5; p. e0300778
• Main Authors: Moin, Abu Tayab, Rani, Nurul Amin, Patil, Rajesh B, Robin, Tanjin Barketullah, Ullah, Md Asad, Rahim, Zahidur, Rahman, Md Foyzur, Zubair, Talha, Hossain, Mohabbat, Mollah, A K M Moniruzzaman, Absar, Nurul, Hossain, Mahboob, Manchur, Mohammed Abul, Islam, Nazneen Naher
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.05.2024; Public Library of Science (PLoS)
• Subjects: Adjuvants; Animals; Antigenic determinants; Antigens; Bioinformatics; Biological & chemical terrorism; Biology and Life Sciences; Care and treatment; Computer Simulation; Contamination; Core protein; Cross-protection; Defensins; Epitope Mapping; Epitopes, B-Lymphocyte - chemistry; Epitopes, B-Lymphocyte - immunology; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Health aspects; Human monkeypox; Humans; Hydrogen; Hydrogen bonding; Hydrogen bonds; Immune response; Lymphocytes; Lymphocytes T; Medical research; Medicine and Health Sciences; Medicine, Experimental; Molecular dynamics; Molecular Dynamics Simulation; Monkeypox; Monkeypox virus - immunology; Mpox (monkeypox) - immunology; Mpox (monkeypox) - prevention & control; Peptide mapping; Peptides; Physical Sciences; Poxviridae - immunology; Proteins; Public health; Smallpox; Stability; T cells; TLR3 protein; Toll-Like Receptor 8 - immunology; Toll-like receptors; Toxicity; Vaccines; Viral infections; Viral Vaccines - immunology; Virions; Virulence (Microbiology); Viruses; Zoonoses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0300778

Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.