Contriving multi-epitope vaccine ensemble for monkeypox disease using an immunoinformatics approach

Abstract

The current global outbreak of monkeypox (MPX) disease, caused by Monkeypox virus (MPXV), has resulted in 16 thousand infection cases, five deaths, and has been declared a global health emergency of international concern by the World Health Organization. Given current challenges in the safety of existing vaccines, a vaccine to prevent MPX infection and/or onset of symptoms would significantly advance disease management. In this context, a multi-epitope-based vaccine could be a well-suited approach. Herein, we searched a publicly accessible database (Virus Pathogen Database and Analysis Resource) for MPXV immune epitopes from various antigens. We prioritized a group of epitopes (10 CD8+ T cells and four B-cell epitopes) using a computer-aided technique based on desirable immunological and physicochemical properties, sequence conservation criteria, and non-human homology. Three multi-epitope vaccines were constructed (MPXV-1–3) by fusing finalized epitopes with the aid of appropriate linkers and adjuvant (beta-defensin 3, 50S ribosomal protein L7/L12, and Heparin-binding hemagglutinin). Codon optimization and in silico cloning in the pET28a (+) expression vector ensure the optimal expression of each construct in the Escherichia Coli system. Two and three-dimensional structures of the constructed vaccines were predicted and refined. The optimal binding mode of the construct with immune receptors [Toll-like receptors (TLR2, TLR3, and TLR4)] was explored by molecular docking, which revealed high docking energies of MPXV-1–TLR3 (–99.09 kcal/mol), MPXV-2–TLR3 (–98.68 kcal/mol), and MPXV-3–TLR2 (–85.22 kcal/mol). Conformational stability and energetically favourable binding of the vaccine-TLR2/3 complexes were assessed by performing molecular dynamics simulations and free energy calculations (Molecular Mechanics/Generalized Born Surface Area method). In silico immune simulation suggested that innate, adaptive, and humoral responses will be elicited upon administration of such potent multi-epitope vaccine constructs. The vaccine constructs are antigenic, non-allergen, non-toxic, soluble, topographically exposed, and possess favourable physicochemical characteristics. These results may help experimental vaccinologists design a potent MPX vaccine.

Deciphering the Immunogenicity of Monkeypox Proteins for Designing the Potential mRNA Vaccine

“…Although some other studies also focused on designing an immunoinformatics-based vaccine against MPXV, the proteins utilized in these studies are different from the protein used in this study. ,, In a similar study, the EEV Type-I membrane glycoprotein was used, but the predicted epitopes are different to those predicted in this study . Similarly, another study predicted the epitope “FSIGGVIHL” and used it for the formulation of the vaccine against MPXV; however, our designed vaccine binds more strongly with the human toll-like receptors as compared to the vaccine designed in that study .…”

Bioinformatics and immunoinformatics assisted multiepitope vaccine construct against Burkholderia anthina

“…S1 . As the hydrogen bonds are important factors and play a vital role in the stability of binding interaction ( Aziz et al, 2022 ). In molecular docking interaction analysis we predicted several hydrogen bonds, which are involved in biding interaction, these bonding are predicted among different amino acids resides of TLR-2 with multi epitopes vaccine construct as presented in Fig.…”

Discovering conserved epitopes of Monkeypox: Novel immunoinformatic and machine learning approaches

“…Similarly, the studies conducted by Akhtar et al utilized the IMV membrane protein L1R and Hemagglutinin for their epitope prediction [ 9 ]. Aziz et al focused on a virulence protein [ 23 ], while Hayat et al employed a chemokine binding protein in their vaccine design [ 24 ].…”