Dominant B cell-T cell epitopes instigated robust immune response in-silico against Scrub Typhus.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8406899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2518 (Electronic) Linking ISSN: 0264410X NLM ISO Abbreviation: Vaccine Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam, The Netherlands : Elsevier Science
      Original Publication: [Guildford, Surrey, UK] : Butterworths, [c1983-
    • Subject Terms:
      Scrub Typhus*/immunology ; Scrub Typhus*/prevention & control ; Orientia tsutsugamushi*/immunology ; Epitopes, B-Lymphocyte*/immunology ; Epitopes, T-Lymphocyte*/immunology ; Vaccines, Subunit*/immunology; Humans ; Molecular Docking Simulation ; Bacterial Vaccines/immunology ; Computer Simulation ; Computational Biology/methods ; T-Lymphocytes, Cytotoxic/immunology ; Machine Learning ; B-Lymphocytes/immunology ; Toll-Like Receptor 2/immunology
    • Abstract:
      Scrub typhus, a potentially life-threatening infectious disease, is attributed to bacteria Orientia tsutsugamushi (O. tsutsugamushi). The transmission of this illness to humans occurs through the bite of infected chiggers, which are the larval forms of mites belonging to the genus Leptotrombidium. In this research, we developed a subunit vaccine specifically designed to target outer membrane proteins. Immunodominant cytotoxic T-lymphocytes (CTLs), B- lymphocytes (BCLs), and major histocompatibility complex (MHC)- II epitopes were identified using machine learning and bioinformatics approaches. These epitopes were arranged in different combinations with the help of suitable linkers like AAY, KK, GPGPG and adjuvant (cholera toxin B) that resulted in a vaccine construct. Physiochemical properties were assessed, where the predicted solubility (0.571) was higher than threshold value. Tertiary structure was predicted using I-TASSER web server and evaluated using Ramachandran plot (94 % residues in most favourable region) and z-score (-6.04), which had shown the structure to have good stability and residue arrangement. Molecular docking with immune receptors, Toll-like receptor (TLR)-2 and -4 showed good residue interaction with 13 and 5 hydrogen bonds respectively. Molecular dynamics simulations of receptor-ligand complex provided the idea about the strong interaction having 1.524751 × 10 -5 eigenvalue. Amino acid sequence of vaccine was converted to nucleotide sequence and underwent codon optimization. The optimized codon sequence was used for in-silico cloning, which provided idea about the possibility of synthesis of vaccine using E. coli as host. Overall, this study provided a promising blueprint for a scrub typhus vaccine, although experimental validation is needed for confirmation. Furthermore, it is crucial to acknowledge that while bioinformatics provides valuable insights, in-vitro and in-vivo studies are imperative for a comprehensive evaluation of vaccine candidate. Thus, the integration of computational predictions with empirical research is essential to validate the efficacy, safety, and real-world applicability of the designed vaccine against Scrub Typhus. Nevertheless, the findings are good to carry forward for in-vitro and in-vivo investigations.
      Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors declare that they don’t have any financial or personal relationship which may considered as competing interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Ltd. All rights reserved.)
    • Contributed Indexing:
      Keywords: BCL; Bioinformatics; CTL; Epitopes; HTL; In-silico; Scrub Typhus; Subunit vaccine
    • Accession Number:
      0 (Epitopes, B-Lymphocyte)
      0 (Epitopes, T-Lymphocyte)
      0 (Vaccines, Subunit)
      0 (Bacterial Vaccines)
      0 (Toll-Like Receptor 2)
    • Publication Date:
      Date Created: 20240508 Date Completed: 20240612 Latest Revision: 20240612
    • Publication Date:
      20240613
    • Accession Number:
      10.1016/j.vaccine.2024.04.082
    • Accession Number:
      38719691