Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis
Arnaud N’Guessan,
Senthilkumar Kailasam,
Fatima Mostefai,
Raphaël Poujol,
Jean-Christophe Grenier,
Nailya Ismailova,
Paola Contini,
Raffaele De Palma,
Carsten Haber,
Volker Stadler,
Guillaume Bourque,
Julie G. Hussin,
B. Jesse Shapiro,
Jörg H. Fritz,
Ciriaco A. Piccirillo
Affiliations
Arnaud N’Guessan
Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; McGill Genome Centre, McGill University, Montréal, QC, Canada
Senthilkumar Kailasam
Canadian Center for Computational Genomics, Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada; Dahdaleh Institute of Genomic Medicine (DIgM), McGill University, Montréal, QC, Canada
Fatima Mostefai
Research Centre, Montreal Heart Institute, Montreal, QC, Canada; Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC, Canada
Raphaël Poujol
Research Centre, Montreal Heart Institute, Montreal, QC, Canada
Jean-Christophe Grenier
Research Centre, Montreal Heart Institute, Montreal, QC, Canada
Nailya Ismailova
Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; McGill University Research Center on Complex Traits (MRCCT), McGill University, Montréal, QC, Canada; Dahdaleh Institute of Genomic Medicine (DIgM), McGill University, Montréal, QC, Canada
Paola Contini
Department of Internal Medicine, University of Genoa and IRCCS IST-Ospedale San Martino, Genoa, Italy
Raffaele De Palma
Department of Internal Medicine, University of Genoa and IRCCS IST-Ospedale San Martino, Genoa, Italy
Carsten Haber
PEPperPRINT GmbH, Heidelberg, Germany
Volker Stadler
PEPperPRINT GmbH, Heidelberg, Germany
Guillaume Bourque
Canadian Center for Computational Genomics, Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada; Dahdaleh Institute of Genomic Medicine (DIgM), McGill University, Montréal, QC, Canada
Julie G. Hussin
Research Centre, Montreal Heart Institute, Montreal, QC, Canada; Département de Médecine, Université de Montréal, Montréal, QC, Canada
B. Jesse Shapiro
Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; McGill Genome Centre, McGill University, Montréal, QC, Canada; Dahdaleh Institute of Genomic Medicine (DIgM), McGill University, Montréal, QC, Canada
Jörg H. Fritz
Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; McGill University Research Center on Complex Traits (MRCCT), McGill University, Montréal, QC, Canada; Dahdaleh Institute of Genomic Medicine (DIgM), McGill University, Montréal, QC, Canada; Corresponding author
Ciriaco A. Piccirillo
Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; McGill University Research Center on Complex Traits (MRCCT), McGill University, Montréal, QC, Canada; Infectious Diseases and Immunity in Global Health Program of the Research Institute of McGill Health Center, Montréal, QC, Canada; Dahdaleh Institute of Genomic Medicine (DIgM), McGill University, Montréal, QC, Canada; Corresponding author
Summary: Here, we exploit a deep serological profiling strategy coupled with an integrated, computational framework for the analysis of SARS-CoV-2 humoral immune responses. Applying a high-density peptide array (HDPA) spanning the entire proteomes of SARS-CoV-2 and endemic human coronaviruses allowed identification of B cell epitopes and relate them to their evolutionary and structural properties. We identify hotspots of pre-existing immunity and identify cross-reactive epitopes that contribute to increasing the overall humoral immune response to SARS-CoV-2. Using a public dataset of over 38,000 viral genomes from the early phase of the pandemic, capturing both inter- and within-host genetic viral diversity, we determined the evolutionary profile of epitopes and the differences across proteins, waves, and SARS-CoV-2 variants. Lastly, we show that mutations in spike and nucleocapsid epitopes are under stronger selection between than within patients, suggesting that most of the selective pressure for immune evasion occurs upon transmission between hosts.
