Design of Multi-Epitope Vaccine from Nipah Virus proteome using Immunoinformatics approach

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Zaki E.A
Mohamed S.B
Hamad S.H
Ali S.S
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Napata College
Background: Nipah virus (NiV) is a zoonotic virus of the paramyxovirus family that sporadically breaks out from livestock and human. Annual review of diseases prioritized under the R&D WHO Blueprint listed the Nipah virus as one of the emerging infectious diseases requiring urgent research and development effort. Moreover, there is a major layback in the development of effective vaccines or drugs against NiV. The aim of this study is to design a non-toxic and potent multi-epitope vaccine against NiV using bioinformatics approach. Materials & Method: In this study, T and B-cell epitopes of NiV protein were predicted and screened based on the antigenicity, toxicity, allergenicity and IFN induction features. The epitopes were linked by suitable linkers. Four different adjuvants were attached to the vaccine constructs, then secondary and the 3D structure of the vaccines was predicted. The refinement process was performed to improve the quality of the 3D model structure; the validation process performed using the Ramachandran plot. The designed vaccines binding affinity to HLA molecules, TLR 8 and TLR were evaluated by molecular docking, and select the best docking score for all vaccines against TLR8. Finally, in silico gene cloning was performed in the pET28a (+) vector. Result: The proposed vaccine was shown to be antigenic in VaxiJen server, non-allergenic in Allertop server and non-toxic in Toxinpred server. Thephysiochemical properties of the vaccine showed constructed vaccines stable and can be soluble overexpression.Regarding MHC-I, predicted epitopes for studied proteins (G, FG, M, N, P, L, V and W) ranged from 6 to 52, with an IC50 from 1 to 100, while in MHC-II, predicted epitopes ranged from 1 to 61 with an IC50 1 to 500. Vaccine tertiary structure was predicted, refined and validated to assess the stability of the vaccine via Ramachandran plot. Moreover, solubility of the vaccine construct was greater than the average solubility provided by protein SOL and SOLpro servers. Disulfide engineering was performed to reduce the high mobile regions in the vaccine to enhance stability which was predicted for the vaccines constructed, except L proposed vaccine which was dispensed. Docking of the vaccine construct with TLR8 showed the best binding energy with all proposed vaccines, TLR8 ligand result was taken for all next studies. Immune-simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells and INF-γ. Upon cloning, the vaccine protein was reverse transcribed into DNA sequence and cloned into pET28a (+) vector to ensure translational potency and microbial expression. Conclusion: The overall results of the study proved that the multi- epitope construct is a potential candidate for an efficient protective vaccine against NiV. The immunoinformatics approaches accelerate vaccine development process to reduce the risk of in vitro pre-clinical trials.