Identification of Highly Conserved SARS-CoV-2 Antigenic Epitopes with Wide Coverage Using Reverse Vaccinology Approach

Abstract

One of the most effective strategies for eliminating new and emerging infectious diseases is effective immunization. The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) warrants the need for a maximum coverage vaccine. Moreover, mutations that arise within the virus have a significant impact on the vaccination strategy. Here, we built a comprehensive in silico workflow pipeline to identify B-cell- and T-cell-stimulating antigens of SARS-CoV-2 viral proteins. Our in silico reverse vaccinology (RV) approach consisted of two parts: (1) analysis of the selected viral proteins based on annotated cellular location, antigenicity, allele coverage, epitope density, and mutation density and (2) analysis of the various aspects of the epitopes, including antigenicity, allele coverage, IFN-γ induction, toxicity, host homology, and site mutational density. After performing a mutation analysis based on the contemporary mutational amino acid substitutions observed in the viral variants, 13 potential epitopes were selected as subunit vaccine candidates. Despite mutational amino acid substitutions, most epitope sequences were predicted to retain immunogenicity without toxicity and host homology. Our RV approach using an in silico pipeline may potentially reduce the time required for effective vaccine development and can be applicable for vaccine development for other pathogenic diseases as well.

Epitope identification of SARS-CoV-2 structural proteins using in silico approaches to obtain a conserved rational immunogenic peptide

“…Currently, numerous projects for the development of effective vaccines have been carried out, and some of these vaccines are already commercially available for humans [45] . However, traditional vaccine production techniques have some disadvantages, which can be overcome by using computational approaches [46] . In addition, recent advances in bioinformatics have provided a variety of tools and servers capable of reducing the cost and time of advancing the traditional vaccine [5] .…”

Bioinformatic analysis of B and T cell epitopes from SARS-CoV-2 Spike, Membrane and Nucleocapsid proteins as a strategy to assess possible cross-reactivity between emerging variants, including Omicron, and other human coronaviruses

“…In total, we identified for S protein 128 CD8 and CD4 T cells epitopes (Figure 2A), 89 for protein M (Figure 2B), and 114 for protein N (Figure 2C). From these, we identified 73 ERIS 36,55,[64][65][66][67][68][69] for S protein, 77 for M protein 59,60,[70][71][72][73][74] and 98 for N protein 36,52,64,70,72,74,75 (Supplementary Table 2). In addition, we were able to compile 9 ECE for S protein [64][65][66][67][68][69]76 , 3…”

“…From these, we identified 73 ERIS 36,55,[64][65][66][67][68][69] for S protein, 77 for M protein 59,60,[70][71][72][73][74] and 98 for N protein 36,52,64,70,72,74,75 (Supplementary Table 2). In addition, we were able to compile 9 ECE for S protein [64][65][66][67][68][69]76 , 3…”

Design of Peptide Vaccine for COVID19: CD8+ and CD4+ T cell epitopes from SARS-CoV-2 open-reading-frame protein variants

“…Since nsp3 is the largest multi-domain protein in SARS-Cov-2, the highest number of experimental epitopes was identified and used in the validation. A total of 169 high quality experimental CD8+ T cell epitopes were retrieved from SARS-CoV-2 T cell epitope database that were previously reported in multiple studies [7,8,[16][17][18][19][20][21][22][23] (Supplementary Table 1) and tested for T cell reactivity. Additional 3 epitopes -ILLLDQALV, WLMWLIINL and CLEASFNYL were identified and selected as highly homological to SARS-CoV-1 genome, having identity of 88.89%, 66.67% and 55.56%, respectively [24].…”

“…Nsp3, the largest multi-domain protein produced by coronaviruses, plays a central role in viral replication, as well as nsp12, which functions as RNA polymerase. ORF3a, the largest accessory protein of 275 amino acids in SARS-CoV-2, also has a significant role in virus pathogenesis and T cell reactivity [7, 8, 9].…”