Immunoinformatics Design of a Multi-Epitope Vaccine Candidate via Poxin-Schlafen Protein of Monkeypox Virus

Background and Objectives: Monkeypox virus, a DNA-enveloped virus of the orthopoxvirus family, causes monkeypox infection in humans.Poxviruses have a distinctive nuclease called poxin, which cleaves cyclic dinucleotide 2'-3'-cGAMP, a crucial secondary messenger in the cGAS-STING (Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes) signaling pathway.Despite existing drugs and vaccines for orthopoxvirus infections, the recent spread of monkeypox has raised global concerns.This study investigated the poxin-schlafen protein of monkeypox virus as a potential target for a novel multi-epitope vaccine. Materials and Methods:This study was conducted using bioinformatic data analysis.Epitopes of this protein were evaluated for nonallergenicity, non-toxicity, and the ability to elicit T and B cell responses.The interaction between the vaccine and toll-like receptor-4 (TLR-4) was assessed using Cluspro 2.0.Immune, and MD simulations were performed to confirm the reliability of the docked complexes. Results:The designed vaccine candidate was highly antigenic, non-allergenic, soluble, and had acceptable physicochemical properties.The three-dimensional structure of the vaccine and its interaction with TLR-4 were elucidated.Molecular dynamics simulations corroborated the high stability of the vaccine-TLR-4 complex.Immune simulation indicated that the vaccine candidate effectively elicited robust protective immune responses in the human body. Conclusion:This study identified the most efficacious epitopes from the poxin-schlafen protein of the monkeypox virus.These findings demonstrate the potential efficacy of this vaccine candidate in eliciting immune responses.This study could significantly advance the development of an antiviral vaccine against monkeypox viruses.However, further in vitro and in vivo studies are required.