Immuno-informatics profiling of monkeypox virus cell surface binding protein for designing a next generation multi-valent peptide-based vaccine

Monkeypox is a viral etiological agent with hallmarks analogous to those observed in smallpox cases in the past. The ongoing outbreak of Monkeypox viral infection is becoming a global health problem. Multi-valent peptide based next generation vaccines provides us a promising solution to combat these emerging infectious diseases by eliciting cell-mediated and humoral immune response. Considering the success rate of subtractive proteomics pipeline and reverse vaccinology approach, in this study, we have developed a novel, next-generation, multi-valent, in silico peptide based vaccine construct by employing cell surface binding protein. After analyzing physiochemical and biological properties of the selected target, the protein was subjected to B cell derived T cell epitope mapping. Iterative scrutinization lead to the identification of two highly antigenic, virulent, non-allergic, non-toxic, water soluble, and Interferon-gamma inducer epitopes i.e. HYITENYRN and TTSPVRENY. We estimated that the shortlisted epitopes for vaccine construction, roughly correspond to 99.74% of the world’s population. UK, Finland and Sweden had the highest overall population coverage at 100% which is followed by Austria (99.99%), Germany (99.99%), France (99.98%), Poland (99.96), Croatia (99.93), Czech Republic (99.87%), Belgium (99.87), Italy (99.86%), China (97.83%), India (97.35%) and Pakistan (97.13%). The designed vaccine construct comprises of 150 amino acids with a molecular weight of 16.97242 kDa. Molecular docking studies of the modelled MEMPV (Multi-epitope Monkeypox Vaccine) with MHC I (PDB ID: 1I1Y), MHC II (PDB ID: 1KG0), and other immune mediators i.e. toll like receptors TLR3 (PDB ID: 2A0Z), and TLR4 (PDB ID: 4G8A) revealed strong binding affinity with immune receptors. Host immune simulation results predicted that the designed vaccine has strong potency to induce immune responses against target pathogen in the form of cellular and antibody-dependent immunity. Our findings suggest that the hypothesized vaccine candidate can be utilized as a potential therapeutic against Monkeypox however experimental study is required to validate the results and safe immunogenicity.