Immunoinformatic-guided novel mRNA vaccine designing to elicit immunogenic responses against the endemic Monkeypox virus

Abstract

Monkeypox virus (MPXV) is an orthopoxvirus, causing zoonotic infections in humans with smallpox-like symptoms. The WHO reported MPXV cases in May 2022 and the outbreak caused significant morbidity threats to immunocompromised individuals and children. Currently, no clinically validated therapies are available against MPXV infections. The present study is based on immunoinformatics approaches to design mRNA-based novel vaccine models against MPXV. Three proteins were prioritized based on high antigenicity, low allergenicity, and toxicity values to predict T- and B-cell epitopes. Lead T- and B-cell epitopes were used to design vaccine constructs, linked with epitope-specific linkers and adjuvant to enhance immune responses. Additional sequences, including Kozak sequence, MITD sequence, tPA sequence, Goblin 5’, 3’ UTRs, and a poly(A) tail were added to design stable and highly immunogenic mRNA vaccine construct. High-quality structures were predicted by molecular modeling and 3D-structural validation of the vaccine construct. Population coverage and epitope-conservancy speculated broader protection of designed vaccine model against multiple MPXV infectious strains. MPXV-V4 was eventually prioritized based on its physicochemical and immunological parameters and docking scores. Molecular dynamics and immune simulations analyses predicted significant structural stability and binding affinity of the top-ranked vaccine model with immune receptors to elicit cellular and humoral immunogenic responses against the MPXV. The pursuance of experimental and clinical follow-up of these prioritized constructs may lay the groundwork to develop safe and effective vaccine against MPXV.

Communicated by Ramaswamy H. Sarma

Keywords:

• Reverse vaccinology
• immunoinformatics
• mRNA vaccine
• multi-epitope vaccine construct
• monkeypox

Acknowledgments

The authors extend their appreciation to King Saud University for funding this work through research supporting project (RSP2023R376), Riyadh, Saudi Arabia.

Author contributions

C.L., A.K., and S.Aiman. conceived the basic idea. S.Aiman., Y.A., A.A., M.A., and S.Ali. performed the analysis and prepared the initial draft. A.M, S.S, S.Akhtar. and A.K. reviewed the critical analysis and helped in draft preparation. A.K. and C.L. finalized the draft and supervised the overall study. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data relevant to this study is provided in the manuscript and its supplementary material file.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.