PMID- 36451670 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221202 IS - 2287-3651 (Print) IS - 2287-366X (Electronic) IS - 2287-3651 (Linking) VI - 11 IP - 3 DP - 2022 Sep TI - Identifying immunodominant multi-epitopes from the envelope glycoprotein of the Lassa mammarenavirus as vaccine candidate for Lassa fever. PG - 249-263 LID - 10.7774/cevr.2022.11.3.249 [doi] AB - 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. CI - (c) Korean Vaccine Society. FAU - Rowaiye, Adekunle Babajide AU - Rowaiye AB AUID- ORCID: 0000-0002-8773-5944 AD - National Biotechnology Development Agency, Abuja, Nigeria. FAU - Nwonu, Ezinne Janefrances AU - Nwonu EJ AUID- ORCID: 0000-0001-8392-9170 AD - National Biotechnology Development Agency, Abuja, Nigeria. FAU - Asala, Titilayo Mercy AU - Asala TM AUID- ORCID: 0000-0003-3464-2936 AD - National Biotechnology Development Agency, Abuja, Nigeria. FAU - Ogu, Amoge Chidinma AU - Ogu AC AUID- ORCID: 0000-0003-3461-2737 AD - National Biotechnology Development Agency, Abuja, Nigeria. FAU - Bur, Doofan AU - Bur D AUID- ORCID: 0000-0001-7625-7118 AD - National Biotechnology Development Agency, Abuja, Nigeria. FAU - Chukwu, Chimaobi AU - Chukwu C AUID- ORCID: 0000-0003-2411-0290 AD - National Biotechnology Development Agency, Abuja, Nigeria. FAU - Oli, Angus Nnamdi AU - Oli AN AUID- ORCID: 0000-0001-8519-2555 AD - Department of Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria. FAU - Agbalalah, Tarimoboere AU - Agbalalah T AUID- ORCID: 0000-0002-5875-4126 AD - National Biotechnology Development Agency, Abuja, Nigeria. AD - Department of Anatomy, Baze University, Abuja, Nigeria. LA - eng PT - Journal Article DEP - 20220930 PL - Korea (South) TA - Clin Exp Vaccine Res JT - Clinical and experimental vaccine research JID - 101592344 PMC - PMC9691867 OTO - NOTNLM OT - Envelope protein OT - Epitopes OT - Lassa virus OT - Major histocompatibility complex OT - Vaccine candidate COIS- No potential conflict of interest relevant to this article was reported. EDAT- 2022/12/02 06:00 MHDA- 2022/12/02 06:01 PMCR- 2022/09/01 CRDT- 2022/12/01 02:24 PHST- 2022/05/26 00:00 [received] PHST- 2022/07/26 00:00 [accepted] PHST- 2022/12/01 02:24 [entrez] PHST- 2022/12/02 06:00 [pubmed] PHST- 2022/12/02 06:01 [medline] PHST- 2022/09/01 00:00 [pmc-release] AID - 10.7774/cevr.2022.11.3.249 [doi] PST - ppublish SO - Clin Exp Vaccine Res. 2022 Sep;11(3):249-263. doi: 10.7774/cevr.2022.11.3.249. Epub 2022 Sep 30.