Abstract
The pandemic caused by SARS-CoV-2 has led to the successful development of effective vaccines however the prospect of variants of SARS-CoV-2 and future coronavirus outbreaks necessitates the investigation of other vaccine strategies capable of broadening vaccine mediated T-cell responses and potentially providing cross-immunity. In this study the SARS-CoV-2 proteome was assessed for clusters of immunogenic epitopes restricted to diverse human leucocyte antigen. These regions were then assessed for their conservation amongst other coronaviruses representative of different alpha and beta coronavirus genera. Sixteen highly conserved peptides containing numerous HLA class I and II restricted epitopes were synthesized from these regions and assessed in vitro for their antigenicity against T-cells from individuals with previous SARS-CoV-2 infection. Monocyte derived dendritic cells were generated from these peripheral blood mononuclear cells (PBMC), loaded with SARS-CoV-2 peptides, and used to induce autologous CD4+ and CD8+ T cell activation. The SARS-CoV-2 peptides demonstrated antigenicity against the T-cells from individuals with previous SARS-CoV-2 infection indicating that this approach holds promise as a method to activate anti-SAR-CoV-2 T-cell responses from conserved regions of the virus which are not included in vaccines utilising the Spike protein.
Highlights
The pandemic caused by the novel coronavirus, SARS-CoV-2, has prompted a global response to produce effective vaccines
peripheral blood mononuclear cells (PBMC) demonstrating responses to a SARS-C oV-2 consensus peptide pool and serum antibody responses to the SARS-C oV-2 spike protein were defined as having been previously infected with SARS-C oV-2 whilst PBMC and sera lacking detectable responses were defined as SARS-CoV-2 naïve
Identification of clusters of epitopes, previously validated for HLA binding or T-cell activation and deposited within the IEDB database, were used. This resulted in the identification of 25 peptide regions harbouring multiple predicted or experimentally validated epitopes. Five of these peptides were identified within the Spike protein and were not investigated further since T-c ell responses to these regions may be raised by existing vaccines
Summary
The pandemic caused by the novel coronavirus, SARS-CoV-2, has prompted a global response to produce effective vaccines. A number of vaccines have been approved for use having demonstrated varying levels of efficacy in clinical trials [1] These vaccines, often based upon targeting the viral Spike protein, responsible for facilitating entry of SARS-CoV-2 into cells [2], have demonstrated an ability to limit infection, transmission and the onset of serious disease. The recent identification of SARS-C oV-2 variants to which vaccine elicited immune protection may be reduced [3] raises the prospect of continued susceptibility to serious infection and the need for repeated vaccination to raise immunity to new variants
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