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

Cell Syst. 2021 Jan 20;12(1):102-107.e4. doi: 10.1016/j.cels.2020.11.010. Epub 2020 Nov 27.


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.

Keywords: SARS-CoV-2; combinatorial optimization; haplotype; machine learning; major histocompatibility complex; peptide vaccine; population coverage; subunit; vaccine augmentation; vaccine evaluation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / immunology*
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / immunology*
  • Forecasting
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology*
  • Machine Learning*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology*


  • COVID-19 Vaccines
  • Vaccines, Subunit