Computationally Optimized SARS-CoV-2 MHC Class I and II Vaccine Formulations Predicted to Target Human Haplotype Distributions

Cell Syst. 2020 Aug 26;11(2):131-144.e6. doi: 10.1016/j.cels.2020.06.009. Epub 2020 Jul 27.

Abstract

We present a combinatorial machine learning method to evaluate and optimize peptide vaccine formulations for SARS-CoV-2. Our approach optimizes the presentation likelihood of a diverse set of vaccine peptides conditioned on a target human-population HLA haplotype distribution and expected epitope drift. Our proposed SARS-CoV-2 MHC class I vaccine formulations provide 93.21% predicted population coverage with at least five vaccine peptide-HLA average hits per person (≥ 1 peptide: 99.91%) with all vaccine peptides perfectly conserved across 4,690 geographically sampled SARS-CoV-2 genomes. Our proposed MHC class II vaccine formulations provide 97.21% predicted coverage with at least five vaccine peptide-HLA average hits per person with all peptides having an observed mutation probability of ≤ 0.001. We provide an open-source implementation of our design methods (OptiVax), vaccine evaluation tool (EvalVax), as well as the data used in our design efforts here: https://github.com/gifford-lab/optivax.

Keywords: COVID-19; SARS-CoV-2; combinatorial optimization; haplotype; machine learning; major histocompatibility complex; peptide vaccine; population coverage; vaccine augmentation; vaccine evaluation.

Publication types

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

MeSH terms

  • Betacoronavirus / genetics
  • Betacoronavirus / immunology*
  • COVID-19 Vaccines
  • Coronavirus Infections / genetics
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology
  • Haplotypes*
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / genetics*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Machine Learning
  • SARS-CoV-2
  • Sequence Analysis, DNA / methods*
  • Sequence Analysis, DNA / standards
  • Vaccines, Subunit / chemistry
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology*
  • Viral Vaccines / chemistry
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • COVID-19 Vaccines
  • Epitopes
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Vaccines, Subunit
  • Viral Vaccines