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Computational design of a multi-epitope mRNA vaccine against orthopoxviruses: A path toward comprehensive poxvirus
Nafiseh Maghsoodi1, Navid Nezafat2, Amin Ramezani1
1Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran.
Abstract:
Along with the recent outbreak of monkeypox (MPOX), there are worries about other outbreaks of the poxvirus genus that threaten global public health. Until now, although there are no specific vaccines for MPOXV, there are no comprehensive vaccines for all dangerous poxviruses. This research utilizes immunoinformatics and structural vaccinology methodologies to develop a multi-epitope mRNA vaccine targeting variola virus (VARV), vaccinia virus (VACV), monkeypox virus (MPOXV), and cowpox virus (CPXV), which are four pathogenic orthopoxviruses (OPV). Accordingly, A29L, M1R, A35R, B6R, and F8L antigens were selected. Then, their sequences were retrieved and aligned to determine the conserved parts of each antigenic region among these four types of viruses. Different immunoinformatic methods were employed for forecasting B-cell, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) epitopes. The epitopes were analyzed through a filtering process that checked for antigenicity, toxicity, allergenicity, and cytokine inducibility. The goal was to find epitopes that can make both T- and B-cells react. The vaccine was constructed and modeled via the trRosetta server. Molecular docking was employed between the epitopes and adjuvant receptors along with MHC type I and II molecules. Subsequently, the best structure with low energy was selected, and molecular dynamics (MD) simulations were performed. The immunological simulation data indicated that the developed vaccine possesses significant potential to provoke both cellular and humoral immune responses. Finally, with in vitro and in vivo experiments in the future, the designed vaccine could be a promising candidate for vaccination against pathogenic poxviruses.
Insights
This study developed a multi-epitope mRNA vaccine using immunoinformatics to target four pathogenic orthopoxviruses (OPV), including monkeypox virus. The vaccine shows potential for broad protection against dangerous poxviruses.
Area of Science:
- Virology
- Immunology
- Vaccine Development
- Bioinformatics
Background:
- Recent monkeypox (MPOX) outbreaks highlight the threat of other poxviruses.
- No comprehensive vaccines exist for all dangerous orthopoxviruses (OPV).
Purpose of the Study:
- To design a multi-epitope mRNA vaccine targeting four pathogenic OPVs: variola virus (VARV), vaccinia virus (VACV), monkeypox virus (MPOXV), and cowpox virus (CPXV).
Main Methods:
- Utilized immunoinformatics and structural vaccinology to identify conserved epitopes from selected viral antigens (A29L, M1R, A35R, B6R, F8L).
- Filtered epitopes for antigenicity, non-toxicity, non-allergenicity, and cytokine inducibility.
- Constructed and modeled the vaccine using trRosetta, followed by molecular docking and molecular dynamics (MD) simulations.
Main Results:
- Identified potential B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes.
- The developed vaccine model demonstrated low energy and stability through MD simulations.
- Immunological simulations indicated significant potential for both cellular and humoral immune responses.
Conclusions:
- The designed multi-epitope mRNA vaccine is a promising candidate for broad protection against pathogenic orthopoxviruses.
- Further in vitro and in vivo studies are warranted to validate its efficacy.
