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

doi:10.1016/j.isci.2023.107394

Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis

iScience. 2023 Jul 13;26(8):107394. doi: 10.1016/j.isci.2023.107394. eCollection 2023 Aug 18.

Authors

Arnaud N'Guessan^{1

2}, Senthilkumar Kailasam^{3

4

5}, Fatima Mostefai^{6

7}, Raphaël Poujol⁶, Jean-Christophe Grenier⁶, Nailya Ismailova^{1

8

5}, Paola Contini⁹, Raffaele De Palma⁹, Carsten Haber¹⁰, Volker Stadler¹⁰, Guillaume Bourque^{3

4

5}, Julie G Hussin^{6

11}, B Jesse Shapiro^{1

2

5}, Jörg H Fritz^{1

8

5}, Ciriaco A Piccirillo^{1

8

12

5}

Affiliations

¹ Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.
² McGill Genome Centre, McGill University, Montréal, QC, Canada.
³ Canadian Center for Computational Genomics, Montréal, QC, Canada.
⁴ Department of Human Genetics, McGill University, Montréal, QC, Canada.
⁵ Dahdaleh Institute of Genomic Medicine (DIgM), McGill University, Montréal, QC, Canada.
⁶ Research Centre, Montreal Heart Institute, Montreal, QC, Canada.
⁷ Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC, Canada.
⁸ McGill University Research Center on Complex Traits (MRCCT), McGill University, Montréal, QC, Canada.
⁹ Department of Internal Medicine, University of Genoa and IRCCS IST-Ospedale San Martino, Genoa, Italy.
¹⁰ PEPperPRINT GmbH, Heidelberg, Germany.
¹¹ Département de Médecine, Université de Montréal, Montréal, QC, Canada.
¹² Infectious Diseases and Immunity in Global Health Program of the Research Institute of McGill Health Center, Montréal, QC, Canada.

Abstract

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.

Keywords: Computational bioinformatics; Immunology; Structural biology; Virology.