Design of a Novel Multi-Epitope mRNA Vaccine against Marburg Virus using Reverse Vaccinology
TL;DR
In silico cloning validated the capacity for effective expression in E. coli and secondary structure revealed that the mRNA vaccine was thermodynamically stable, which may contribute to the development of an experimental MARV vaccine.
Abstract
Aim: The Marburg virus (MARV), a zoonotic pathogen, causes a severe hemorrhagic fever for which no approved vaccine currently exists. Methods: This study used reverse vaccinology to develop a multi-epitope vaccine against Marburg virus (MARV). To improve stability and translational efficiency, the construct was modified as an mRNA vaccine by adding a 5′ cap, 5′ UTR, Kozak sequence, tPA signal peptide, 3′ UTR, and poly(A) tail. Results: We selected the potential 06 CTL, 06 HTL, and 04 LBL epitopes with high antigenicity, no allergenicity, and no toxicity, and the epitopes were linked with the linkers (GPGPG, AAY, KK) and an adjuvant (β-defensin 2). The designed vaccine showed an antigenic score of 0.7189 with promising properties. Molecular docking reveals that the vaccine exhibits a strong binding affinity with human TLR4 (-1301.5 kcal/mol). Meanwhile, MD simulation confirms its structural stability, and immune simulations indicate robust cellular and humoral immune responses. Ultimately, in silico cloning validated the capacity for effective expression in E. coli. Finally, secondary structure revealed that the mRNA vaccine (-418.59 kcal/mol) was thermodynamically stable. These outcomes may contribute to the development of an experimental MARV vaccine. Conclusions: However, further experimental evaluation is necessary to assess the efficacy of the modified mRNA vaccine for MARV prevention.