Immunoinformatics-Based Multi-Epitope Vaccine Design for the Re-Emerging Monkeypox Virus

"Background
On May 7, 2022, WHO reported a new monkeypox case. By May 2023 over 80,000 cases had been reported worldwide outside previously endemic nations. (This primarily affected the men who have sex with men (MSM) community in rich nations). The present research aims to develop a multi-epitope vaccine for the monkeypox virus (MPXV) using structural and cell surface proteins.

Methods
The first part of the research involved retrieving protein sequences. The Immune Epitope Database (IEDB) was then used to analyze the B and T lymphocyte epitopes. After analyzing the sensitizing properties, toxicity, antigenicity, and molecular binding, appropriate linkers were utilized to connect selected epitopes to adjuvants, and the structure of the vaccine was formulated. Algorithms from the field of immunoinformatics predicted the secondary and tertiary structures of vaccines. The physical, chemical, and structural properties were refined and validated to achieve maximum stability. Molecular docking and molecular dynamic simulations were subsequently employed to assess the vaccine’s efficacy. Afterward, the ability of the vaccine to interact with toll-like receptors 3 and 4 (TLR3 and TLR4) was evaluated. Finally, the optimized sequence was then introduced into the Escherichia coli (E. coli) PET30A + vector.

Results
An immunoinformatics evaluation suggested that such a vaccine might be safe revealed that this vaccine is safe, hydrophilic, temperature- and condition-stable, and can stimulate innate immunity by binding to TLR3 and TLR4.

Conclusion
Our findings suggest that the first step in MPXV pathogenesis is structural and cell surface epitopes. In this study, the most effective and promising epitopes were selected and designed through precision servers. Furthermore, through the utilization of multi-epitope structures and a combination of two established adjuvants, this research has the potential to be a landmark in developing an antiviral vaccine against MPXV. However, additional in vitro and in vivo tests are required to confirm these results."