Subunit epitope vaccine prediction against SARS-CoV-2 using Transmembrane and C-terminal domains of envelope protein

Abstract

Abstract Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global pandemic in recent times. SARS-CoV-2 is an enveloped beta-coronavirus. Epitope prediction against viruses for subunit vaccine development using immunoinformatic approaches is becoming a common practice. Currently available vaccines are designed against entire proteins. However, in present study, two domains of enveloped protein, named Transmembrane (TM) and C terminal domain (CTD) of the Delta variant were targeted for their potential immunogenic responses. Methods: Proteomic Sequences for both domains for the years 2020-2022 were retrieved and subjected to conservation and mutational analyses. Their physio-chemical characteristics were also determined. The epitopes for T Cell, B Cell, and cytotoxic T lymphocyte were predicted and checked for allergic properties Phosphorylation & glycosylation sites were determined. Secondary and tertiary structural conformations were predicted and screened for potential cleavage sites. Finally, a vaccine construct was designed using the selected peptides based on their best antigenicity, immunogenicity, conservation, and physiochemical properties. Results: A total of 102 residual substitutions were found, including 3, 4, and 95 for the sequences of years 2020, 2021, and 2022 respectively. The residual and atomic composition of domains sequences were analyzed. The maximum amino acid flexibility was found at residue 60 (serine), and the maximum transmembrane tendency was found at positions 14, 15, and 16 (alanine, phenylalanine, & valine). Physio-chemical analysis confirmed the probable antigenicity and absence of allergenic properties of our predicted epitopes. Primarily, a total of 34 B Cell, 20 T Cell, and 3 CTL epitopes were predicted. Following rigorous validations like antigenicity and allergenicity assessment, 15 B Cell, 14 T Cell and 2 CTL epitopes were selected. These conserved and potential antigenic epitopes were then combined to create a vaccine construct, which can be used independently or alongside some other subunit/peptide cocktail formulation to address the challenges associated with using whole protein regions of the virus or mRNA-based vaccines. Conclusion: This study suggested that TM & CTD domains of envelope protein of SARS-CoV-2 might serve as potential antigens and proposed an effective alternative vaccine approach using smaller viral domains cocktail to avoid post-vaccination complications associated with whole viral protein-based vaccines.