Immunoinformatics-driven design of a multi-epitope vaccine for effective protection against Machupo virus

The Arenaviridae family of viruses includes the Machupo virus (MACV), which is associated with the potentially fatal Bolivian hemorrhagic fever, a disease with a mortality rate of 15%-30% depending on the speed of diagnosis and the availability of health facilities. To date, there is no licensed vaccine available for MACV, highlighting the need for a preventive measure. In this work, we use immunoinformatics approaches to create a multi-epitope vaccine based on the most dominant MACV proteins. For constructational epitopes, we selected glycoprotein precurssor (GP), nucleoprotein (NP), RNA-dependant RNA polymerase (L), and Zinc-binding RING finger protein (Z) from garner the proteins essential for replicating and invading a host cell. Using in silico prediction methods, a total of thirteen T-cell epitopes (seven MHC class I and six MHC class II binders) and eight B-cell epitopes were identified as having the greatest potential to elicit strong and broad-spectrum immune responses. These selected epitopes were validated in silico to ensure the highest degree of immunogenicity and no allergenic or toxic effects. To increase the potential of the vaccine to elicit an immune response, the 50S ribosomal protein L7/L12 was added as an adjuvant. The analysis of population coverage indicated that the epitopes could provide immunological protection to nearly 98.04% of the world population. The theoretical vaccine design included 3D modeling and simulation of docking to immunoreceptors like Toll-like receptor 4 (TLR4) and MHC molecules, which confirmed their stable and high-affinity binding interactions. The results from in silico simulations of the immune response also showed abundant production of antibodies and strong engagement of various T-cell subsets. In summary, this study proposes a multi-epitope Machupo virus vaccine candidate that can be tested in the lab to evaluate its effectiveness as a preventative measure for Bolivian hemorrhagic fever.