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Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis
Arnaud N'Guessan1,2, Senthilkumar Kailasam3,4,5, Fatima Mostefai6,7
1Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.
Iscience
|August 21, 2023
Summary
This study maps SARS-CoV-2 immune responses using deep serological profiling and computational analysis. It reveals pre-existing immunity hotspots and identifies mutations under selection pressure during transmission, crucial for understanding viral evolution and immune evasion.
Area of Science:
- Immunology
- Virology
- Computational Biology
Background:
- Understanding SARS-CoV-2 humoral immunity is vital for vaccine and therapeutic development.
- Pre-existing immunity and viral evolution impact SARS-CoV-2 pathogenesis.
Purpose of the Study:
- To analyze SARS-CoV-2 humoral immune responses using deep serological profiling.
- To identify B cell epitopes and their evolutionary and structural properties.
- To investigate pre-existing immunity and cross-reactivity to SARS-CoV-2.
Main Methods:
- High-density peptide array (HDPA) spanning SARS-CoV-2 and endemic coronaviruses.
- Integrated computational framework for analyzing serological data.
- Analysis of over 38,000 viral genomes to determine epitope evolutionary profiles.
Main Results:
- Identification of B cell epitopes, including hotspots of pre-existing immunity.
- Discovery of cross-reactive epitopes contributing to the overall immune response.
- Epitope mutations show stronger selection between hosts than within, indicating immune evasion during transmission.
Conclusions:
- Deep serological profiling provides insights into SARS-CoV-2 humoral immunity.
- Viral evolution and pre-existing immunity shape the immune response.
- Immune evasion pressure is primarily exerted during host-to-host transmission.
