Developing a Subunit Vaccine against SARS-CoV-2 Using Bioinformatics Insights on Cytotoxic T-Lymphocytes (CTLs) Epitopes

Muhammad Usama Saeed, Hamid Bashir, Nazim Hussain, Amjad Nawaz, Muhammad Adnan Ali, Ajaz Ahmad, Saiful Malook, Qurban Ali

Article ID: 7566
Vol 37, Issue 10, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233710.550
Received: 8 November 2023; Accepted: 8 November 2023; Available online: 8 November 2023; Issue release: 8 November 2023

Abstract

Background: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates urgent solutions. Despite extensive clinical investigations and trials, no approved treatment has been found. To address this critical need, we designed a study to create and validate a subunit vaccine against SARS-CoV-2 based on cytotoxic T-lymphocyte (CTL) epitopes, using various immunoinformatics tools to gain essential insights into the associated immune responses. Methods: We focused on the spike region of SARS-CoV-2, vital for its survival and virulence, to identify potential antigenic CTL epitopes. Our predictions suggested that these epitopes could significantly stimulate cell-mediated immunity. We selected a sequence comprising three antigenic and nontoxic CTL epitopes to enhance the safety and immunogenicity of the final vaccine. We predicted the three-dimensional (3D) structure of the vaccine and conducted docking studies with human major histocompatibility complex 1 (MHC-1) and toll-like receptor-3 (TLR-3) receptors. Molecular dynamics (MD) simulations were performed to confirm the stability of the vaccine binding with these receptors. Additionally, in-silico Polymerase Chain Reaction (PCR) and cloning were conducted to evaluate the amplification and protein expression of the final vaccine. Results: Molecular docking studies showed strong binding between the vaccine construct and the human leukocyte antigen (HLA)-A heavy alpha chain of MHC-1 and the C-terminal domain of TLR-3 receptors. MD simulations in an explicit system further confirmed the robust and stable binding of CTL epitopes with MHC-1 and TLR-3 receptors. Using computational cloning based on SnapGene, excellent protein expression was achieved in the pET-28b(+) plasmid. Conclusions: The findings of this study strongly support the manufacturing and in vitro and in vivo investigations of this vaccine to evaluate its effectiveness as a therapy for COVID-19.


Keywords

COVID-19;vaccine;in-silico design;treatment;SARS-CoV-2;molecular docking


References

Supporting Agencies



Copyright (c) 2023 Muhammad Usama Saeed, Hamid Bashir, Nazim Hussain, Amjad Nawaz, Muhammad Adnan Ali, Ajaz Ahmad, Saiful Malook, Qurban Ali




This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).