Bridging One Health: Computational design of a multi-epitope messenger RNA vaccine for cross-species immunization against Nipah virus

Abstract

Background and Aim: Nipah virus (NiV) poses a threat to human and animal health, particularly swine, which serve as primary vectors for human transmission. Despite its severe risks, no NiV vaccine currently exists for humans or animal hosts; thus, innovative vaccine development approaches that address cross-species transmission are required. This study was computationally designed to evaluate a multi-epitope messenger RNA (mRNA) vaccine targeting NiV for human and swine immunization. Materials and Methods: B and T lymphocyte epitopes were identified from NiV structural proteins using multiple epitope prediction tools. All epitopes were linked to form a multi-epitope construct, and various adjuvant combinations were analyzed for physicochemical properties and immune simulation. Molecular docking and dynamics were employed to visualize the construct’s interaction with a host immune receptor. Signal peptides were added to the construct, and mRNA sequences were generated using LinearDesign. The minimum free energies (MFEs) and codon adaptation indices (CAI) were used to select the final mRNA sequence of the vaccine construct. Results: Computational tools predicted 10 epitopes within NiV structural proteins that can be recognized by human and swine immune receptors. The construct with β-defensin 2 adjuvant was selected as the final immunogenic region after showing favorable immunogenicity profiles and physicochemical properties. The final vaccine sequence had higher MFE and CAI compared to the BioNTech/Pfizer BNT162b2 and Moderna mRNA-1273 vaccines. Conclusion: The multi-epitope mRNA vaccine designed in this study shows promising results as a potential NiV vaccine candidate. Further in vivo and in vitro studies are required to confirm the efficacy. Keywords: computational design, cross-species immunization, messenger RNA vaccine, multi-epitope, Nipah virus.