Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2

Infect Dis Poverty. 2020 Sep 16;9(1):132. doi: 10.1186/s40249-020-00752-w.

Abstract

Background: Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19.

Methods: Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV.

Results: Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression.

Conclusion: The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.

Keywords: COVID-19; Epitope; Immunoinformatics; Multiepitope-based subunit vaccine; SARS-CoV-2; Structural protein; Vaccine.

MeSH terms

  • Betacoronavirus / immunology*
  • COVID-19
  • COVID-19 Vaccines
  • Coronavirus Infections / genetics
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control*
  • Epitopes, B-Lymphocyte / chemistry
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Humans
  • Immunogenicity, Vaccine / immunology
  • Molecular Docking Simulation
  • Pandemics / prevention & control*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / prevention & control*
  • SARS-CoV-2
  • Sequence Analysis, Protein
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Toll-Like Receptor 3 / chemistry
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / immunology
  • Vaccines, Subunit / chemistry
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Vaccinology / methods
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology
  • Viral Vaccines / chemistry
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • COVID-19 Vaccines
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Spike Glycoprotein, Coronavirus
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Vaccines, Subunit
  • Viral Matrix Proteins
  • Viral Vaccines
  • membrane protein, SARS-CoV-2
  • spike protein, SARS-CoV-2