Harnessing immunoinformatics for the rational design of mRNA vaccines against the emerging Junin virus

Junin virus (JUNV) is a zoonotic virus and is the main cause of Argentine hemorrhagic fever (AHF). Despite the availability of the Candid#1 live-attenuated vaccine, safety concerns and limited accessibility necessitate the development of a safer, more effective alternative. This study employed computational and bioinformatics approaches to design a multi-epitope mRNA vaccine targeting JUNV glycoproteins. Antigenic glycoprotein sequences were retrieved and screened for Linear B-cell (LBL), cytotoxic T-cell (CTL), and helper T-cell (HTL) epitopes, ensuring high antigenicity, non-toxicity, and non-allergenicity. Eight B-cell, fifteen CTL, and five HTL epitopes were selected based on high antigenicity, non-allergenicity, and non-toxicity. Population coverage analysis revealed an 88.19% global coverage, suggesting broad vaccine applicability. The designed vaccine constructs incorporated immunogenic linkers and 50S ribosomal protein L7/L12 as an adjuvant to enhance immune activation. Physicochemical and post-translational modification analyses confirmed the stability, structural integrity, and immunogenic potential of the constructs. Molecular docking and molecular dynamics (MD) simulations demonstrated strong and stable interactions with TLR4, MHCI, MHCII, and CTL2 receptors, essential for effective immune stimulation. Codon optimization and mRNA secondary structure analysis ensured efficient expression and stability in human cells. Finally, in silico immune simulation predicted robust humoral and cellular immune responses, characterized by high IgG and IgM titers, cytokine production (IFN-γ, IL-4, IL-10), and memory B-cell activation, confirming long-term immunity. These findings highlight the potential of the designed mRNA vaccine for effective JUNV immunization, warranting further in vitro and in vivo validation for clinical application. [Abstract copyright: © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2026. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.]