A new study has introduced a computationally designed peptide-based vaccine candidate targeting the monkeypox virus (MPXV), using the virus’s membrane glycoprotein to guide epitope selection. The research, led by scientists at the University of North Bengal in collaboration with multiple international institutions, was published online in Current Medicinal Chemistry.
Using immunoinformatics tools, the team designed a multi-epitope construct that demonstrated strong predicted binding to human immune receptors and favorable immune activation in simulation models. While further laboratory testing is needed, the findings represent a promising direction in the search for next-generation monkeypox vaccines, particularly those that could be produced efficiently and tailored to global populations.
Targeting Viral Surface Proteins to Inform Vaccine Design
The vaccine candidate focuses on MPXV’s membrane glycoprotein—a surface protein essential for host cell entry and a potential target for neutralizing immune responses. From a strain linked to international travel, researchers identified multiple B-cell and T-cell epitopes with high predicted immunogenicity and low allergenic or toxic potential.
Specifically, the construct integrates three B-cell epitopes, four MHC class I, and two MHC class II T-cell epitopes, linked together with immune-compatible spacers. The design also incorporates β-defensin I and the PADRE sequence as adjuvants to boost innate and adaptive immune responses.
Binding Simulations Indicate Receptor Engagement
To evaluate how the vaccine might perform in a host immune environment, the team performed molecular docking studies with Toll-Like Receptor 3 (TLR3), a pattern recognition receptor involved in antiviral responses. The candidate showed a favorable binding affinity of –17.2 kcal/mol, and molecular dynamics simulations over 500 nanoseconds confirmed complex stability.
These results suggest that the designed construct could be effectively recognized by the immune system—though confirmation will require laboratory validation.
Simulated Immune Response and Global Applicability
In silico immune simulations projected strong primary and secondary immune responses, with elevated levels of immunoglobulins (IgG1, IgM), memory T-cell activation, and cytokines such as IFN-γ and IL-2. These findings indicate the potential for both humoral and cellular protection against MPXV.
The selected T-cell epitopes also mapped to common HLA alleles, providing an estimated global population coverage of 80.89%. This suggests the candidate could be broadly relevant across regions and genetic backgrounds—an important consideration for global deployment.
Expression Potential and Production Readiness
To evaluate the candidate’s manufacturability, the authors performed codon optimization for E. coli expression systems. The construct achieved a Codon Adaptation Index of 1.0 and a GC content of 51.4%, indicating high potential for protein expression. In silico cloning into the pET28a(+) vector further supports the feasibility of laboratory-scale production.
Relevance for Public Health Security
Monkeypox virus continues to present a health threat globally, with over 124,000 mpox cases and ongoing outbreaks reported by the World Health Organization. While existing vaccines like JYNNEOS are approved for emergency use, there remain gaps in global supply, efficacy in some populations, and long-term durability.
Computational design approaches such as this offer a cost-effective and rapid pathway for identifying viable candidates that may complement existing countermeasures. By focusing on a novel target and leveraging multi-epitope peptide technology, this study contributes to a broader effort to strengthen the global response to orthopoxvirus threats.
Outlook and Research Needs
Though the vaccine construct shows strong predicted properties, it remains in the preclinical research phase. The next steps include laboratory expression, in vitro immunogenicity studies, and eventually in vivo testing to assess efficacy, safety, and durability.
As with all computational vaccine designs, experimental confirmation will be critical. However, the methodical pipeline demonstrated here—combining antigen prediction, immune simulation, and expression modeling—provides a solid foundation for further development.
Mishra, S.K., Priya, P., Basit, A., et al. Designing of Peptide Vaccine by Investigating Monkeypox Virus Membrane Glycoprotein: An Integrated In Silico and Immunoinformatics Approach. Current Medicinal Chemistry. 9 July 2025.
Editor’s Note: The disease caused by monkeypox virus is now officially called mpox, following a 2022 renaming by the World Health Organization to reduce stigma and improve public communication. While mpox refers to the illness, monkeypox virus (MPXV) remains the accepted scientific name for the virus itself.