Machine learning-enhanced immunopeptidomics applied to T-cell epitope discovery for COVID-19 vaccines.

Journal: Nature communications
PMID: 39609459

Abstract

Next-generation T-cell-directed vaccines for COVID-19 focus on establishing lasting T-cell immunity against current and emerging SARS-CoV-2 variants. Precise identification of conserved T-cell epitopes is critical for designing effective vaccines. Here we introduce a comprehensive computational framework incorporating a machine learning algorithm-MHCvalidator-to enhance mass spectrometry-based immunopeptidomics sensitivity. MHCvalidator identifies unique T-cell epitopes presented by the B7 supertype, including an epitope from a + 1-frameshift in a truncated Spike antigen, supported by ribosome profiling. Analysis of 100,512 COVID-19 patient proteomes shows Spike antigen truncation in 0.85% of cases, revealing frameshifted viral antigens at the population level. Our EpiTrack pipeline tracks global mutations of MHCvalidator-identified CD8 + T-cell epitopes from the BNT162b4 vaccine. While most vaccine epitopes remain globally conserved, an immunodominant A*01-associated epitope mutates in Delta and Omicron variants. This work highlights SARS-CoV-2 antigenic features and emphasizes the importance of continuous adaptation in T-cell vaccine development.

Authors

  • Kevin A Kovalchik
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • David J Hamelin
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Peter Kubiniok
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Benoîte Bourdin
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Fatima Mostefai
    Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
  • Raphaël Poujol
    Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
  • Bastien Paré
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Shawn M Simpson
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • John Sidney
    La Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, San Diego, California 92037 USA.
  • Éric Bonneil
    Institute of Research in Immunology and Cancer, Montreal, QC, Canada.
  • Mathieu Courcelles
    Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada.
  • Sunil Kumar Saini
    Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark.
  • Mohammad Shahbazy
    Department of Biochemistry and Molecular Biology and Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.
  • Saketh Kapoor
    Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Vigneshwar Rajesh
    Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Maya Weitzen
    Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Jean-Christophe Grenier
    Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
  • Bayrem Gharsallaoui
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Loïze Maréchal
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Zhaoguan Wu
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Christopher Savoie
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Alessandro Sette
    La Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, San Diego, California 92037 USA.
  • Pierre Thibault
    From the ‡Institute for Research in Immunology and Cancer, pierre.thibault@umontreal.ca md.tyers@umontreal.ca.
  • Isabelle Sirois
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
  • Martin A Smith
    RNA Biology and Plasticity Group, Garvan Institute of Medical Research, 384 Victoria Street, Sydney, NSW 2010, Australia. m.smith@garvan.org.au.
  • Hélène Decaluwe
    Centre Hospitalier de l'Université (CHU) Ste Justine, Centre de Recherche, Montreal, QC, Canada.
  • Julie G Hussin
    Department of Medicine, Montreal Heart Institute, Montreal, Quebec, Canada; Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada; Mila - Québec AI Institute, Montreal, Quebec, Canada.
  • Mathieu Lavallée-Adam
    Department of Biochemistry, Microbiology and Immunology and Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
  • Etienne Caron
    CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada. etienne.caron@yale.edu.

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