Development of a multi-epitope mRNA vaccine candidate for oropouche virus: an in-silico approach for immune response...

Oropouche fever, caused by the Oropouche virus (OROV), presents an emerging health threat, particularly in tropical regions, due to its severe impact on human health and the lack of available vaccines. Since its initial identification in Trinidad and Tobago in 1955, OROV has led to multiple outbreaks across South America. This study aims to develop a multi-epitope-based mRNA vaccine construct for OROV using in-silico methodologies. We identified potential T-cell, B-cell, and helper T-cell epitopes from selected OROV proteins, prioritizing those that are non-allergenic, non-toxic, antigenic, and capable of inducing both humoral and cell-mediated immune responses across diverse populations. Molecular docking was employed to assess interactions between selected epitopes and MHC alleles. Twelve epitopes, a tPA signal peptide, the RpfE adjuvant, and specific linkers were assembled into the mRNA vaccine construct. Immune simulations indicated favorable immunogenicity in humans. Codon optimization and in silico cloning demonstrated efficient mRNA translation in human cells and successful vector integration. Further molecular docking and dynamics simulations with TLR-4 and TLR-3 confirmed the stability and interaction of the vaccine construct with immune receptors. These findings suggest that the proposed vaccine could be a promising candidate for OROV prevention, pending further in vitro and in vivo validation.

The online version contains supplementary material available at 10.1007/s40203-025-00470-x.