{"title":"Identifying immunodominant multi-epitopes from the envelope glycoprotein of the Lassa mammarenavirus as vaccine candidate for Lassa fever.","authors":"Adekunle Babajide Rowaiye, Ezinne Janefrances Nwonu, Titilayo Mercy Asala, Amoge Chidinma Ogu, Doofan Bur, Chimaobi Chukwu, Angus Nnamdi Oli, Tarimoboere Agbalalah","doi":"10.7774/cevr.2022.11.3.249","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC).</p><p><strong>Materials and methods: </strong>The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropriate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engineering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector.</p><p><strong>Results: </strong>A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubility upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimated half-life greater than 10 hours in <i>Escherichia coli</i> and showed stability in all the parameters of MDS.</p><p><strong>Conclusion: </strong>The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.</p>","PeriodicalId":51768,"journal":{"name":"Clinical and Experimental Vaccine Research","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/22/cevr-11-249.PMC9691867.pdf","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Vaccine Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.7774/cevr.2022.11.3.249","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/30 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 1
Abstract
Purpose: Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC).
Materials and methods: The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropriate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engineering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector.
Results: A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubility upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimated half-life greater than 10 hours in Escherichia coli and showed stability in all the parameters of MDS.
Conclusion: The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.
期刊介绍：
Clin Exp Vaccine Res, the official English journal of the Korean Vaccine Society, is an international, peer reviewed, and open-access journal. It covers all areas related to vaccines and vaccination. Clin Exp Vaccine Res publishes editorials, review articles, special articles, original articles, case reports, brief communications, and correspondences covering a wide range of clinical and experimental subjects including vaccines and vaccination for human and animals against infectious diseases caused by viruses, bacteria, parasites and tumor. The scope of the journal is to disseminate information that may contribute to elaborate vaccine development and vaccination strategies targeting infectious diseases and tumors in human and animals. Relevant topics range from experimental approaches to (pre)clinical trials for the vaccine research based on, but not limited to, basic laboratory, translational, and (pre)clinical investigations, epidemiology of infectious diseases and progression of all aspects in the health related issues. It is published printed and open accessed online issues (https://ecevr.org) two times per year in 31 January and 31 July. Clin Exp Vaccine Res is linked to many international databases and is made freely available to institutions and individuals worldwide
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