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Immunoinformatic design of a COVID-19 subunit vaccine using entire structural immunogenic epitopes of SARS-CoV-2.

ABSTRACT: Coronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease's associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Potential non-toxic and non-allergenic T-cell and B-cell binding and cytokine inducing epitopes were then identified through a priori prediction. Selected epitopes were bound to each other with appropriate linkers, followed by appending a suitable adjuvant to increase the immunogenicity of the vaccine polypeptide. Molecular modelling of the 3D structure of the vaccine construct, docking, molecular dynamics simulations and free energy calculations confirmed that the vaccine peptide had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. As our vaccine polypeptide design captures the advantages of structural epitopes and simultaneously integrates precautions to avoid relevant side effects, it is suggested to be promising for elicitation of an effective and safe immune response against SARS-CoV-2 in vivo.

SUBMITTER: Behmard E

PROVIDER: S-EPMC7704662 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Immunoinformatic design of a COVID-19 subunit vaccine using entire structural immunogenic epitopes of SARS-CoV-2.

Behmard Esmaeil E Soleymani Bijan B Najafi Ali A Barzegari Ebrahim E

Scientific reports 20201130 1

Coronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease's associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extr ...[more]

PMID: 33257716

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Project description:The world has faced unprecedented disruptions like global quarantine and the COVID-19 pandemic due to SARS-CoV-2. To combat these unsettling situations, several effective vaccines have been developed and are currently being used. However, the emergence of new variants due to the high mutation rate of SARS-CoV-2 challenges the efficacy of existing vaccines and has highlighted the need for novel vaccines that will be effective against various SARS-CoV-2 variants. In this study, we exploited the four structural proteins of SARS-CoV-2 to execute a potential multi-epitope vaccine against SARS-CoV-2 and its variants. The vaccine was designed by utilizing the antigenic, non-toxic, and non-allergenic B-cell and T-cell epitopes, which were selected from conserved regions of viral proteins. To build a vaccine construct, epitopes were connected through different linkers and an adjuvant was also attached at the start of the construct to enhance the immunogenicity and specificity of the epitopes. The vaccine construct was then screened through the aforementioned filters and it scored 0.6019 against the threshold of 0.4 on VexiJen 2.0 which validates its antigenicity. Toll-like receptors (i.e., TLR2, TLR3, TLR4, TLR5, and TLR8) and vaccine construct were docked by Cluspro 2.0, and TLR8 showed strong interaction with construct having a maximum negative binding energy of - 1577.1 kCal/mole. C-IMMSIM's immune simulations over three doses of the vaccine and iMODS' molecular dynamic simulations were executed to assess the reliability of the docked complexes. The stability of the vaccine construct was evaluated through the physicochemical analyses and the findings suggested that the manufactured vaccine is stable under a wide range of circumstances and can trigger immune responses against various SARS-CoV-2 variants (due to conserved epitopes). However, to strengthen the formulation of the vaccine and assess its safety and effectiveness, additional investigations and studies are required to support the computational data of this research at in-vitro and in-vivo levels.Supplementary informationThe online version contains supplementary material available at 10.1007/s40203-023-00156-2.

Project description:A novel infectious agent, SARS-CoV-2, is responsible for causing the severe respiratory disease COVID-19 and death in humans. Spike glycoprotein plays a key role in viral particles entering host cells, mediating receptor recognition and membrane fusion, and are considered useful targets for antiviral vaccine candidates. Therefore, computational techniques can be used to design a safe, antigenic, immunogenic, and stable vaccine against this pathogen. Drawing upon the structure of the S glycoprotein, we are trying to develop a potent multi-epitope subunit vaccine against SARS-CoV-2. The vaccine was designed based on cytotoxic T-lymphocyte and helper T-lymphocyte epitopes with an N-terminal adjuvant via conducting immune filters and an extensive immunoinformatic investigation. The safety and immunogenicity of the designed vaccine were further evaluated via using various physicochemical, allergenic, and antigenic characteristics. Vaccine-target (toll-like receptors: TLR2 and TLR4) interactions, binding affinities, and dynamical stabilities were inspected through molecular docking and molecular dynamic (MD) simulation methods. Moreover, MD simulations for dimeric TLRs/vaccine in the membrane-aqueous environment were performed to understand the differential domain organization of TLRs/vaccine. Further, dynamical behaviors of vaccine/TLR systems were inspected via identifying the key residues (named HUB nodes) that control interaction stability and provide a clear molecular mechanism. The obtained results from molecular docking and MD simulation revealed a strong and stable interaction between vaccine and TLRs. The vaccine's ability to stimulate the immune response was assessed by using computational immune simulation. This predicted a significant level of cytotoxic T cell and helper T cell activation, as well as IgG, interleukin 2, and interferon-gamma production. This study shows that the designed vaccine is structurally and dynamically stable and can trigger an effective immune response against viral infections.

Dataset Information

Immunoinformatic design of a COVID-19 subunit vaccine using entire structural immunogenic epitopes of SARS-CoV-2.

Publications

Immunoinformatic design of a COVID-19 subunit vaccine using entire structural immunogenic epitopes of SARS-CoV-2.

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