Computational Modeling and Evaluation of Potential mRNA and Peptide-Based Vaccine against Marburg Virus (MARV) to
Faisal F Albaqami1, Ali Altharawi2, Hassan N Althurwi1
1Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Abstract:
A hemorrhagic fever caused by the Marburg virus (MARV) belongs to the Filoviridae family and has been classified as a risk group 4 pathogen. To this day, there are no approved effective vaccinations or medications available to prevent or treat MARV infections. Reverse vaccinology-based approach was formulated to prioritize B and T cell epitopes utilizing a numerous immunoinformatics tools. Potential epitopes were systematically screened based on various parameters needed for an ideal vaccine such as allergenicity, solubility, and toxicity. The most suitable epitopes capable of inducing immune response were shortlisted. Epitopes with population coverage of 100% and fulfilling set parameters were selected for docking with human leukocyte antigen molecules, and binding affinity of each peptide was analyzed. Finally, 4 CTL and HTL each while 6 B cell 16-mers were used for designing multiepitope subunit (MSV) and mRNA vaccine joined via suitable linkers. Immune simulations were used to validate the constructed vaccine's capacity to induce a robust immune response whereas molecular dynamics simulations were used to confirm epitope-HLA complex stability. Based on these parameter's studies, both the vaccines constructed in this study offer a promising choice against MARV but require further experimental verification. This study provides a rationale point to begin with the development of an efficient vaccine against Marburg virus; however, the findings need further experimental validation to confirm the computational finding of this study.
Insights
Computational methods identified promising vaccine candidates for Marburg virus (MARV) disease. This study designed multiepitope subunit and mRNA vaccines, offering a potential new strategy against this deadly filovirus.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Marburg virus (MARV) causes severe hemorrhagic fever and is a significant global health threat.
- Currently, no approved vaccines or treatments exist for MARV infections.
- MARV is a risk group 4 pathogen within the Filoviridae family.
Purpose of the Study:
- To develop novel vaccine candidates against Marburg virus using a reverse vaccinology approach.
- To identify and prioritize B and T cell epitopes for vaccine design.
- To computationally design and validate multiepitope subunit (MSV) and mRNA vaccines.
Main Methods:
- Utilized immunoinformatics tools to screen potential B and T cell epitopes.
- Assessed epitopes for allergenicity, solubility, and toxicity, prioritizing those with 100% population coverage.
- Performed molecular docking with human leukocyte antigen (HLA) molecules and analyzed binding affinities.
- Designed MSV and mRNA vaccines using selected epitopes and linkers, validated by immune and molecular dynamics simulations.
Main Results:
- Shortlisted optimal epitopes capable of inducing a robust immune response.
- Successfully designed MSV and mRNA vaccine constructs targeting MARV.
- Computational simulations confirmed the potential efficacy and stability of the designed vaccines.
- Identified 4 CTL, 4 HTL, and 6 B cell epitopes for vaccine formulation.
Conclusions:
- The computationally designed MSV and mRNA vaccines show promise as potential countermeasures against Marburg virus.
- This study provides a strong rationale for further experimental validation of these vaccine candidates.
- Further research is required to confirm the efficacy of these novel vaccine strategies in preclinical and clinical settings.
