Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein

Abstract

The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development, and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus-neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. This study predicted several potential T cell epitopes with web-based analytic tools and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants and compatible with a presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

In Silico Screening of Prospective MHC Class I and II Restricted T-Cell Based Epitopes of the Spike Protein of SARS-CoV-2 for Designing of a Peptide Vaccine for COVID-19

“…Here, it is worth mentioning that different mutations in positions such as N501, K444, G446, S477 and N439 are reported to enhance the affinity of these residues towards the binding of human ACE2 receptor [26,40]. In accordance with our study, a few recently published articles also documented the promising role of spike protein and T-cell-based epitopes in vaccine design for COVID-19 infection [41,42]. A recently published article by Zannella et al, 2022, showed that synthesized peptides from the selected nucleotide sequences of the genome of coronaviruses were not found to be toxic to the cultured cells and also had resistant properties against serum proteases.…”

A DNA Vaccine Encoding the Full-Length Spike Protein of Beta Variant (B.1.351) Elicited Broader Cross-Reactive Immune Responses against Other SARS-CoV-2 Variants

“…pWT was constructed by inserting a full-length spike-coding gene of SARS-CoV-2 into the pVAX1 vector, which was named the pGX9501 described in the previous publication [ 38 ]. pWT (pGX9501) was proven to induce potent humoral, cellular immunity, and a protective effect after a wild-type SARS-CoV-2 challenge in hACE2 transgenic mice [ 39 ].…”

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

“…Based on the conservancy, antigenicity, allergenicity, population coverage and transmembrane location, another study chose potential conserved epitopes from the S1 (FNATRFASVYAWNRK, 342–356 aa) ( Table 1 ), S2 (FLHVTYVPAQEKNFT, 1062–1072 aa) ( Table 2 ) and the E/M protein to construct a SARS-CoV-2 vaccine and revealed that it had high immunogenicity and broad neutralizing activity against the SARS-CoV-2 RBD ( Figure 3 ) [ 118 ]. Jiang et al, with web-based analytic tools, also predicted potential T cell epitopes induced by the SARS-CoV-2 SP and narrowed them down to CD4 or CD8 T cell epitopes using ELIspot and a cytolytic assay [ 119 ]. In their observation, YYVGYLQPRTFLLKY (264–278 aa), located at the end of the NTD and the upstream of the RBD, is highly conserved among 11 variants of SARS-CoV-2 VOCs and variants of interest (VOIs) and could induce the T cells.…”

“…In their observation, YYVGYLQPRTFLLKY (264–278 aa), located at the end of the NTD and the upstream of the RBD, is highly conserved among 11 variants of SARS-CoV-2 VOCs and variants of interest (VOIs) and could induce the T cells. Further studies also suggested that these epitopes could be well recognized by most HLA alleles globally [ 119 ].…”