Vaccinomics strategy for developing a unique multi-epitope monovalent vaccine against Marburg marburgvirus

摘要

Marburg virus is known to cause a severe hemorrhagic fever (MHF) in both humans and non-human primates with high degree of infectivity and lethality. To date no approved treatment is available for Marburg virus infection. A study was employed to design a novel chimeric subunit vaccine against Marburg virus by adopting reverse vaccinology approach. The entire viral proteome was retrieved from UniprotKB and assessed to design highly antigenic epitopes by antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. Envelope glycoprotein (GP) and matrix protein (VP40) were identified as most antigenic viral proteins which generated a plethora of epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. Physicochemical and secondary structure of the designed vaccine was assessed to ensure its thermostability, hydrophilicity, theoretical PI and structural behaviors. Disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope monovalent vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR8 receptor present on lymphocyte cells demonstrated higher interaction. Moreover, disulfide engineering served to lessen the high mobility region of the designed vaccine in order to extend its stability. Complexed structure of the modeled vaccine and TLR8 showed minimal deformability at molecular level. Finally, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for E. coli strain K12. However, further in vitro and in vivo investigation could be implemented for the acceptance and validation of the predicted vaccine against Marburg virus.