Arnaud N’Guessan
PhD student at the University of Toronto
Senthilkumar Kailasam, PhD
Bioinformatician at McGill University
The CEIRR CMC holds bi-monthly research tutorials that feature leading researchers who develop state-of-the-art computational methods to better understand respiratory viruses. These events are designed to facilitate in-depth discussions and provide ample opportunity for questions from the audience, with each tutorial lasting 1 hour and 30 minutes.
After you register, click on the Eventbrite event page for a zoom link.
Abstract
Background: One prevailing view in our understanding of COVID-19 immunopathogenesis is that an underlying immune response toward endemic human coronaviruses (hCoVs) is a hallmark feature of SARS-CoV-2-infected asymptomatic individuals. However, it is not clear to what extent protein conservation between SARS-CoV-2 and hCoVs could affect adaptive immunity through cross-reactivity. Conserved residues associated with the humoral immune response could also be considered for vaccine design. Indeed, mutations in epitopes have the potential to decrease the effectiveness of adaptive immunity conferred by infection or vaccination. It is also not clear if selection for immune evasion acts on SARS-CoV-2 at the within-host level, or mainly upon transmission similarly to influenza.
Methods: To better understand the adaptive immunity to SARS-CoV-2, we exploited a high-density peptide array (HDPA) spanning the whole hCoVs and SARS-CoV-2 proteomes. We identified B cell epitopes recognized by distinct antibody isotypes in patients’ blood sera of COVID-19-positive and COVID-19-negative patients. We then subjected our data to an integrated computational pipeline to evaluate the fine immunological properties of detected SARS-CoV-2 epitopes and relate them to their evolutionary and structural characteristics.
Results: We captured epitopes that are computationally predicted to be in linear and conformational B-cell epitopes yielding a more complete view of the humoral response. We also highlight hotspots of pre-existing immunity and a subset of cross-reactive epitopes that contribute to increasing the average humoral immune response to SARS-CoV-2. Next, using a dataset of over 38,000 publicly available genome sequences collected during the first two waves of the pandemic, we tracked single nucleotide variants (SNVs) within and between COVID-19 patients and found evidence for positive selection on nonsynonymous mutations in epitopes. Selection for immune evasion occurs mostly upon transmission between hosts. Finally, wave 2-specific SNVs reached higher frequencies across samples compared to wave 1-specific SNVs, consistent with increased selection for immune evasion over time as the number of vaccinated and infected individuals increased.
Significance: We provided data and an analysis framework to validate models of evolution and immunity for SARS-CoV-2. These results have implications for future genomic surveillance and vaccine design.
Note: CEIRR CMC events are open only to CEIRR participants. The meeting and discussion are confidential.