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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.06.027805 doi: bioRxiv preprint these sets, of which 36 (97.2%) had a negative assay result, as predicted. Further, we sought to 1 determine whether our highly predicted SARS-CoV-2 peptide-HLA-I allele pairs (percent rank 2 lower than 1%) would be validated by reported T cell assay results. Despite the significantly 3 smaller number of peptide-MHC allele pairs that were tested for T cell reactivity in the validation 4 dataset, 10 assayed pairs were also highly predicted by our HLA-I binding predictor. Nine out of 5 these 10 (90%) predicted pairs had a positive result to the T cell assay. No low-scoring pairs 6 (percent rank of 50% or above) were reported in the validation dataset. These findings demonstrate The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.06.027805 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.06.027805 doi: bioRxiv preprint A small number of peptides predicted to bind multiple HLA-I and HLA-II alleles can provide 1 broad population coverage 2 The concordance between the validation dataset and our highly predicted peptide-MHC allele pairs 3 indicate that the HLA binding predictors from RECON significantly expand the list of predicted 4 MHC binding peptides from the ORFs of SARS-CoV-2. We then sought to estimate the minimal 5 number of HLA-I and HLA-II epitopes that would be required to provide coverage for the USA, 6 European and Asian Pacific Islander populations based on the prevalence of MHC alleles in these 7 populations (32). We found that a subset of the peptides was predicted to bind a broad set of either 8 HLA-I or HLA-II alleles. We determined that a vaccine containing three of these HLA-I and four