Computational Modeling and Evaluation of Potential mRNA and Peptide‐Based Vaccine against Marburg Virus (MARV) to Provide Immune Protection against Hemorrhagic Fever

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.

Bioinformatic, Biochemical, and Immunological Mining of MHC Class I Restricted T Cell Epitopes for a Marburg Nucleoprotein Microparticle Vaccine

“…Several reverse vaccinology or immunoinformatic (in silico only) studies of Marburg structural proteins have been recently published [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. The bulk of these studies limited their characterization of potential T cell epitopes to the envelope glycoproteins, VP 24 matrix protein, VP30 transcription factor, VP35 polymerase cofactor, and VP matrix protein of MARV [ 46 , 51 , 56 , 57 ]. However, two studies reported on potential HLA class I or class II-restricted T cell epitopes within the MARV nucleoprotein [ 49 , 55 ].…”

“…Recently, the Marburg proteome was screened to identify potential immunogenic epitopes that bind to human MHC molecules. However, previous reports have focused solely on bioinformatics and in silico screening studies [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ] for human MHC molecules. Our contribution involves a bioinformatics analysis of potential immunogenic T cell epitopes specific to human MHC class I (i.e., HLA–A and B) and Cynomolgus MHC class I (Mafa MHC–A).…”