Computational design of a universal vaccine mRNA vaccine for mammarenaviruses

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Abstract
Mammarenaviruses are important zoonotic pathogens that cause serious diseases, such as Lassa fever and Argentine hemorrhagic fever. These diseases continue to threaten global public health, yet vaccines and therapeutic options remain limited. Accordingly, developing a broadly effective vaccine for mammarenaviruses remains a pressing priority. In this work, we systematically analyzed the sequences of the main structural proteins of ten mammarenaviruses. We combined antigenic epitopes from the Immune Epitope Database (IEDB) and used inverse vaccination and immunoinformatics methods to screen for highly conserved B-cell and T-cell epitopes with strong immunogenicity. We then added the tissue plasminogen activator (tPA), the most effective vaccine against these pathogens. To construct a multi-epitope fusion mRNA vaccine candidate, we included the tPA signal peptide, the PADRE adjuvant, and linkers. The mRNA sequence was optimized by advanced algorithms. We assessed the structural stability and immunogenicity of the candidate vaccine using molecular docking, molecular dynamics(MD) simulation, and immunosimulation. The results exhibited that the designed vaccine had good antigenicity and structural stability. It formed stable complexes with a variety of intrinsic immunoreceptors and triggered a strong, sustained, and comprehensive immune response in immunosimulation. This demonstrated its potential as a universal vaccine candidate for mammarenaviruses. In summary, we developed and validated a universal vaccine for mammarenavirus using computerized methods. However, further real-world studies are needed to validate these results.

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