Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and Their Augmentation by Compact Peptide Sets

Subunit vaccines induce immunity to a pathogen by presenting a component of the pathogen and thus inherently limit the representation of pathogen peptides for cellular immunity-based memory. We find that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit peptides may not be robustly displayed by the major histocompatibility complex (MHC) molecules in certain individuals. We introduce an augmentation strategy for subunit vaccines that adds a small number of SARS-CoV-2 peptides to a vaccine to improve the population coverage of pathogen peptide display. Our population coverage estimates integrate clinical data on peptide immunogenicity in convalescent COVID-19 patients and machine learning predictions. We evaluate the population coverage of 9 different subunits of SARS-CoV-2, including 5 functional domains and 4 full proteins, and augment each of them to fill a predicted coverage gap.