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New Multi-Epitope Mpox Vaccine Shows Strong Potential in Silico

July 8, 2025

A new computational vaccine blueprint from University of Dhaka researchers offers promise against monkeypox (mpox), leveraging reverse vaccinology to design a multi-epitope vaccine (MEV) targeting conserved MPXV proteins. In silico modeling revealed strong immune receptor binding and robust T- and B-cell responses, marking a potential leap beyond existing smallpox-based formulations. However, while the immunoinformatics approach is timely amid the Clade Ib resurgence in Africa, no experimental validation has yet been conducted. Further in vitro and in vivo testing is essential before clinical viability can be assessed. This research underscores the power of bioinformatics in pandemic preparedness and next-generation vaccine development.

With mpox resurging in Central Africa and global cases surpassing 124,000, a novel study from the University of Dhaka brings timely innovation: a multi-epitope vaccine (MEV) design grounded in computational biology. Published in Biochemistry and Biophysics Reports, the study uses reverse vaccinology and immunoinformatics to construct a candidate vaccine tailored specifically to the monkeypox virus (MPXV), moving beyond current smallpox-based alternatives like JYNNEOS.

The MEV incorporates validated cytotoxic and helper T-cell epitopes from orthopoxviruses and B-cell epitopes from key MPXV glycoproteins, joined with immunostimulatory adjuvants (β-defensin 3, PADRE, Hp91) to enhance immune response. Structural modeling and molecular docking revealed strong binding affinities to Toll-like receptors (TLR-2 and TLR-4), essential to innate immunity activation. In silico immune simulations predicted durable antibody and T-cell memory responses, along with elevated IFN-γ and IL-2—critical for antiviral defense.

Yet the study acknowledges that experimental hurdles remain. No laboratory or animal model validation has yet been completed, and protein expression was modeled in E. coli, which may not accurately replicate post-translational modifications in vivo. Protein solubility and stability also require empirical testing before advancing toward clinical development.

Nevertheless, this computational MEV framework is a strategic step forward in rational vaccine design—especially relevant for biodefense and pandemic response. If validated, it could represent a more targeted, adaptable solution to mpox and other orthopox threats, especially in low-resource settings with limited vaccine access. As the virus evolves and pressure mounts for scalable interventions, this study underscores the importance of marrying bioinformatics with experimental virology to accelerate vaccine readiness for emerging global health threats.

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