Abstract
SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4+ T cell activation by the antigen-HLA molecule complex.
Highlights
SARS-CoV-2 causes COVID-19, a disease that has become a global pandemic[1,2]
High antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo
There are two key factors for a vaccine to be effective: first, there should be a good match with a HLA Class II molecule, and second, the antigen should be adequately immunogenic, assuming that the individual is immunocompetent for antibody production
Summary
SARS-CoV-2 causes COVID-19, a disease that has become a global pandemic[1,2]. there is an urgent need to develop an effective vaccine against the virus. The key agents for specific immunity and antibody production are the HLA Class II molecules These bind to ~18-22-mer AA peptides resulting from the cleavage of the viral proteins by proteases in antigen presenting cells (APC), which include macrophages[4]. An individual carries 6 classical Class II alleles (2 from each DRB1, DQB1 and DPB1 genes)[4] If these provide a good match to the peptide, the antibody production process starts immediately and, assuming that the person is immunocompetent, antibodies will be produced in time to eliminate the virus and protect from future exposures to that virus. In this study, we examined systematically and exhaustively the SARS-CoV-2 virus spike glycoprotein to determine the binding affinities of epitopes to 66 common HLA Class II alleles and identify regions in the protein with high such affinities as good candidates for vaccine development. Specific attention has been directed towards the spike glycoprotein of the SARSCoV-2 since it represents a major binding site for cells via their ACE2 receptors in a number of recent studies that even revealed its crystal structure[2,9,10]
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