Identification of conserved CD8+ T cell epitopes in Nipah virus towards vaccine development using an immunoinformatics approach

利用免疫信息学方法鉴定尼帕病毒中保守的CD8+ T细胞表位,以用于疫苗研发

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Abstract

PURPOSE: Developing a treatment for Nipah virus (NiV) infection is necessary due to its high fatality rate, broad host range, and unavailable licensed effective treatment. Therefore, this study aimed to identify candidate epitopes of NiV proteins as immunotherapeutic agents for vaccine development. MATERIALS AND METHODS: Immunoinformatics was used to identify conserved fragments and candidate CD8+ epitopes in all 6 structural (F, G, L, M, N, and P) and 2 of 3 nonstructural proteins (V and W). Potential cross-reactivity, toxicity, and allergenicity were assessed. The population coverage of each candidate epitope globally and in high-risk regions were analyzed. Selected epitope-human leukocyte antigen (HLA) pairs were docked to analyze binding energy and spontaneity and favorability of complex formation. RESULTS: Conservation analysis of proteins F, G, L, M, N, P, V, and W resulted in 16, 11, 40, 8, 14, 41, 10, and 10 conserved fragments (≥ nonamer), respectively. One hundred and fifty-three conserved CD8+ epitopes are promiscuous binders and are likely to be good major histocompatibility complex I binders (inhibitory concentration 50 <500 nM), non-toxic, non-allergenic, and non-cross-reactive with human antigens (E-value >1.0e-30). The 3 epitopes with the highest population coverage are (187)YMIPRTMLEF(196) (Global=69.77%, Indonesia=49.69%, Malaysia=5.38%, Philippines=88.44%), (62)YMYLICYGF(70) (Philippines=88.44%) from M, and (809)ATIPFLFLSAY(819) (India=53.86%, Thailand=66.25%) from L. Molecular docking of selected CD8+ epitopes with HLA I allele binders showed favorable and spontaneous complex formation. CONCLUSION: Results showed promising CD8+ T cell epitopes among the structural and nonstructural proteins of NiV, that possess safety, immunogenicity, and broad population coverage.

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