The Monkeypox virus (MPXV), an emerging zoonotic orthopoxvirus, has reemerged as a major global health threat, with the 2022 outbreak predominantly associated with Clade IIb lineages. The surface glycoprotein B21R (OPG210), a major virulence and immune-evasion factor, contains three lineage-defining amino acid substitutions (D209N, P722S, and M1741I) that distinguish Clade IIb from other variants, emphasizing its relevance as a vaccine target. In this study, an integrated immunoinformatics and molecular dynamics-based approach was employed to design a multi-epitope vaccine (MEV) targeting the B21R glycoprotein. Comprehensive B-cell, helper T-lymphocyte (HTL), and cytotoxic T-lymphocyte (CTL) epitopes were screened based on their immune-eliciting potential, non-allergenicity, cytotoxicity and global immunogenic coverage, and were subsequently assembled into a rationally engineered MEV construct. The modeled vaccine displayed potential affinity and conformational integrity in complex with immune receptors, as confirmed by molecular docking, normal mode analysis, and molecular dynamics simulations, which indicated favorable flexibility and compactness conducive to immune activation. By integrating clade-specific sequence variations, this study introduces a strain adapted vaccine design framework capable of addressing viral evolution and immune escape in contemporary MPXV strains. These findings highlight the potential of computational vaccinology as a rapid and cost-effective strategy for mpox vaccine design; however, further experimental and preclinical validation is required.
Tariq et al. (2026) studied this question.