In silico design and validation of a novel multi-epitope vaccine candidate against structural proteins of Chikungunya virus using comprehensive immunoinformatics analyses

Abstract

Chikungunya virus (CHIKV) is an emerging viral infectious agent with the potential of causing pandemic. There is neither a protective vaccine nor an approved drug against the virus. The aim of this study was design of a novel multi-epitope vaccine (MEV) candidate against the CHIKV structural proteins using comprehensive immunoinformatics and immune simulation analyses. In this study, using comprehensive immunoinformatics approaches, we developed a novel MEV candidate using the CHIKV structural proteins (E1, E2, 6 K, and E3). The polyprotein sequence was obtained from the UniProt Knowledgebase and saved in FASTA format. The helper and cytotoxic T lymphocytes (HTLs and CTLs respectively) and B cell epitopes were predicted. The toll-like receptor 4 (TLR4) agonist RS09 and PADRE epitope were employed as promising immunostimulatory adjuvant proteins. All vaccine components were fused using proper linkers. The MEV construct was checked in terms of antigenicity, allergenicity, immunogenicity, and physicochemical features. The docking of the MEV construct and the TLR4 and molecular dynamics (MD) simulation were also performed to assess the binding stability. The designed construct was non-allergen and was immunogen which efficiently stimulated immune responses using the proper synthetic adjuvant. The MEV candidate exhibited acceptable physicochemical features. Immune provocation included prediction of HTL, B cell, and CTL epitopes. The docking and MD simulation confirmed the stability of the docked TLR4-MEV complex. The high-level protein expression in the Escherichia coli (E. coli) host was observed through in silico cloning. The in vitro, in vivo, and clinical trial investigations are required to verify the findings of the current study.