Exploring computational approaches to design mRNA Vaccine against vaccinia and Mpox viruses

Abstract

Background: Messenger RNA (mRNA) vaccines emerged as a powerful tool in the fight against infections. Unlike traditional vaccines, this unique type of vaccine elicits robust and persistent innate and humoral immune response with a unique host cell-mediated pathogen gene expression and antigen presentation.

Methods: This offers a novel approach to combat poxviridae infections. From the genome of vaccinia and Mpox viruses, three key genes (E8L, E7R, and H3L) responsible for virus attachment and virulence were selected and employed for designing the candidate mRNA vaccine against vaccinia and Mpox viral infection. Various bioinformatics tools were employed to generate (B cell, CTL, and HTL) epitopes, of which 28 antigenic and immunogenic epitopes were selected and are linked to form the mRNA vaccine construct. Additional components, including a 5' cap, 5' UTR, adjuvant, 3' UTR, and poly(A) tail, were incorporated to enhance stability and effectiveness. Safety measures such as testing for human homology and in silico immune simulations were implemented to avoid autoimmunity and to mimics the immune response of human host to the designed mRNA vaccine, respectively. The mRNA vaccine's binding affinity was evaluated by docking it with TLR-2, TLR-3, TLR-4, and TLR-9 receptors which are subsequently followed by molecular dynamics simulations for the highest binding one to predict the stability of the binding complex.

Results: With a 73% population coverage, the mRNA vaccine looks promising, boasting a molecular weight of 198 kDa and a molecular formula of C₈₉₀₁H₁₃₆₀₉N₂₄₃₁O₂₆₁₁S₄₈ and it is said to be antigenic, nontoxic and nonallergic, making it safe and effective in preventing infections with Mpox and vaccinia viruses, in comparison with other insilico-designed vaccine for vaccinia and Mpox viruses.

Conclusions: However, further validation through in vivo and in vitro techniques is underway to fully assess its potential.

Keywords: Mpox virus; Pox viruses; immunoinformatics; mRNA vaccine; vaccine design; vaccinia virus.

Figure 1

Flowchart representing the overall mRNA vaccine design processes.

Figure 2

Schematic representation of the mRNA final vaccine construct.

Figure 3

Secondary structure of the mRNA vaccine construct.

Figure 4

Predicted population coverage of the mRNA vaccine construct.

Figure 5

(A) Predicted tertiary structure of Mpox mRNA vaccine construct. (B) Tertiary structure refinement of Mpox mRNA vaccine construct.

Figure 6

(A and B) Ramachandran plot and z‐score graph representing tertiary structure validation.

Figure 7

Molecular dynamics simulation for the vaccine construct. (A) The root mean square deviation. (B) Root mean square fluctuations. (C) Radius of gyration. (D) Number of Hydrogen atoms interactions in the simulation.