In silico design of multi-epitope vaccines against the hantaviruses by integrated structural vaccinology and molecular modeling approaches

PLoS One. 2024 Jul 23;19(7):e0305417. doi: 10.1371/journal.pone.0305417. eCollection 2024.

Abstract

Hantaviruses are single-stranded RNA viruses belonging to the family Bunyaviridae that causes hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) worldwide. Currently, there is no effective vaccination or therapy available for the treatment of hantavirus, hence there is a dire need for research to formulate therapeutics for the disease. Computational vaccine designing is currently a highly accurate, time and cost-effective approach for designing effective vaccines against different diseases. In the current study, we shortlisted highly antigenic proteins i.e., envelope, and nucleoprotein from the proteome of hantavirus and subjected to the selection of highly antigenic epitopes to design of next-generation multi-epitope vaccine constructs. A highly antigenic and stable adjuvant was attached to the immune epitopes (T-cell, B-cell, and HTL) to design Env-Vac, NP-Vac, and Com-Vac constructs, which exhibit stronger antigenic, non-allergenic, and favorable physiochemical properties. Moreover, the 3D structures were predicted and docking analysis revealed robust interactions with the human Toll-like receptor 3 (TLR3) to initiate the immune cascade. The total free energy calculated for Env-Vac, NP-Vac, and Com-Vac was -50.02 kcal/mol, -24.13 kcal/mol, and -62.30 kcal/mol, respectively. In silico cloning, results demonstrated a CAI value for the Env-Vac, NP-Vac, and Com-Vac of 0.957, 0.954, and 0.956, respectively, while their corresponding GC contents were 65.1%, 64.0%, and 63.6%. In addition, the immune simulation results from three doses of shots released significant levels of IgG, IgM, interleukins, and cytokines, as well as antigen clearance over time, after receiving the vaccine and two booster doses. Our vaccines against Hantavirus were found to be highly immunogenic, inducing a robust immune response that demands experimental validation for clinical usage.

MeSH terms

  • Computer Simulation
  • Epitopes / chemistry
  • Epitopes / immunology
  • Hantavirus Infections / immunology
  • Hantavirus Infections / prevention & control
  • Humans
  • Models, Molecular
  • Molecular Docking Simulation
  • Orthohantavirus* / immunology
  • Vaccinology / methods
  • Viral Vaccines* / immunology

Substances

  • Viral Vaccines
  • Epitopes

Grants and funding

This work was supported by Qatar National Research Fund [grant No. NPRP14S-0406-210150] and Qatar University grant No. QUPD-CPH-23/24-592. The statements made herein are solely the responsibility of the authors. Open Access funding is provided by the Qatar National Library. Thank you to the authors for the collaborative work and their cooperation. We would extend our thanks to National University of Medical Sciences for providing us a platform to facilitate present study.