Sequence-based prediction of vaccine targets for inducing T cell responses to SARS-CoV-2 utilizing the bioinformatics predictor RECON

Asaf Poran; Dewi Harjanto; Matthew Malloy; Michael S. Rooney; Lakshmi Srinivasan; Richard B. Gaynor

Unlike HLA-I, which has a closed binding groove that constrains bound peptide lengths to 3 approximately 8 to 12 amino acids, peptides binding HLA-II have a wider length distribution (up 4 to 30 amino acids or even longer) since the HLA-II binding groove is open at both ends. Peptides 5 bind with a 9 amino acid subsequence (termed the binding core) occupying the HLA-II binding 6 groove, with any flanking sequence overhanging the edges of the molecule. We consider a group 7 of peptides that differ in the flanking regions but share a common binding core as a single epitope. 8 Using the HLA-II predictor we identified 7,207 unique binding-cores that are predicted to bind at 9 least one HLA-II allele with a percent rank score of 1% or lower. The number of high-quality 10 peptide-MHC allele pairs we identify per SARS-CoV-2 gene is listed in Table 1 . The majority of 11 predicted peptide-MHC allele pairs are from orf1a and orf1ab, primarily driven by the length of 12 these ORFs. In addition, orf1a and orf1ab have very similar sequences, with over 18,000 identical 13 binding peptide-HLA-I allele pairs predicted for both ORFs. We therefore opted to exclude 14 redundant predictions and only reported unique pairs (see * in Table 1 ). Similarly, all HLA-II 15 predicted epitopes from orf1a were covered by those reported for orf1ab. 16 To test the validity of the SARS-CoV-2 predicted peptide-HLA pairs, we looked for identical 17 peptide sequences in the Coronaviridae portion of the ViPR database ( Figure 2D) . A total of 368 18 HLA-I peptide-MHC allele pairs from SARS-CoV-2 had both a percent rank lower than 1% by 19 our predictor and were found in the HLA-I MHC-binding validation dataset. Strikingly, of these 20 HLA-I peptide-MHC allele pairs, 328 (89.1%) had a positive assay result. As a comparison, we 21 also tested for overlap between epitopes predicted to have low likelihood of MHC-binding (percent 22 rank 50% or higher) and the validation dataset. 37 peptide-MHC allele pairs overlapped between 23 author/funder. All rights reserved. No reuse allowed without permission.