Neoantigen quality and vaccine response
tumour
TUMOUR
To model neoantigen quality, we adapted our previously described modelPrevious versions of our quality modelTo now extend the notion of the cross-reactivity or epitope distance beyond the single substitution case as previously describedWe now took as our two components, in the context of vaccination, how far a neopeptide is from the germline and how close it is to known antigenic IEDB epitopes. For a given 9-mer minimal neoepitope, We defined the quality of a neopeptide as the average quality over the two highest quality 9-mer subsequences that include the substituted residue and are predicted binders (threshold of 4,000 nM) to the HLA type of the individual. As a vaccine can induce neoantigen expression in excess of endogenous expression in a tumour, we dropped the differential MHC presentation term and relaxed our MHC binding cut-off.To determine whether neoantigen quality correlated with immunogenicity of neoantigenic peptides included in the vaccines used in this study, we classified the neopeptides from the 