Proteome conserved multi-epitope-based vaccine construct against Nipah virus

Nipah virus (NiV) is a highly pathogenic virus with no available FDA-approved medication. Herein, immunoinformatic-based approaches may serve as a crucial method for rapid development of vaccine targeting the emerging strains of the NiV. The study utilizes immunoinformatic-based computational methodology to design multi-epitope subunit vaccine by deciphering highly conserved antigenic epitopes across NiV strains. The NiV whole proteome (UP000002330) was subjected to shortlist immune epitopes based on high antigenic scores, non-allergenic status, broad HLA population coverage, and 100% conservancy across three different demographic NiV strains. The obtained primary sequence of the MEVC construct was then 3D modelled using AlphaFold2 server and validated through PROSA web analysis. The interaction profile of the proposed multi-epitope-based vaccine construct and immune receptor TLR3 was also explored with molecular docking and normal mode analysis. The conformational stability of the complex was confirmed through a triplicate of 200-ns molecular dynamics simulation. Finally, in silico cloning construct and immune simulation data for the proposed vaccine were also depicted. The results revealed a total of 12 highly antigenic and non-allergenic epitopes comprising of 4 T-cell, 4 B-cell, and 4 HTL demonstrating a high population coverage (> 90%) and 100% conservancy across the three studied strains. The 3D validated structure of the proposed vaccine through molecular docking studies suggested a stronger total binding free energy of - 62.83 (kcal/mol) and formation of 10 hydrogen bonds, 2 salt bridges, and 10 hydrophobic interactions with human TLR3 structure. The NMA analysis showed minimal fluctuations of the complex and an eigenvalue of 3.96 × 10^-6. Molecular dynamics simulations exhibited stable complexes with RMSD and RMSF values ranging from 0 to 20. The optimal vaccine sequence was computationally cloned into the pET-28a (+) vector and immune simulation depicted an organized immune response with elevated levels of IgG1 and IgG2, activated T- and B-cell populations, and potential memory cell development. The study provides baseline data, and a 3D validated design of a novel MEVC-NIPAH vaccine through multi-scale computational analysis. Further experimental validations will be required to clarify the protective efficacy and potential translation of the proposed vaccine into clinical settings.