A deeper understanding of the molecular determinants that drive humoral responses to coronaviruses, and in particular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is critical for improving and developing diagnostics, therapies and vaccines. Moreover, viral variants have the potential of mutating key antigens in a manner that alters the ability of the immune system to detect and clear infections. In this study, Dr. Fritz, Dr. Piccirillo et al. exploit a deep serological profiling strategy coupled with an integrated, computational framework for the analysis of SARS-CoV-2 humoral immune responses of asymptomatic or recovered COVID-19-positive patients relative to COVID-19-negative patients. The authors made use of a novel high-density peptide array (HDPA) spanning the entire proteomes of SARS-CoV-2 and endemic human coronaviruses to rapidly identify B cell epitopes recognized by distinct antibody isotypes in patients’ blood sera. Using their integrated computational pipeline, the authors then evaluated the fine immunological properties of detected SARS-CoV-2 epitopes and relate them to their evolutionary and structural properties. While some epitopes are common across all hCoVs, others are private to specific hCoVs. The authors also highlight the existence of hotspots of pre-existing immunity and identify a subset of cross-reactive epitopes that contributes to increasing the overall humoral immune response to SARS-CoV-2. Using a large public dataset of over 38,000 samples from the early phase of the pandemic, allowing to capture inter- and within-host genetic viral diversity, the authors determined the evolutionary profile of epitopes and the differences across proteins, waves and SARS-CoV-2 variants, which have important implications for genomic surveillance and vaccine design. Lastly, the authors show that mutations in S and N epitopes emerge more rapidly upon transmission rather than within patients suggesting that most of the selective pressure for immune evasion following SARS-CoV-2 infection occurs upon transmission between hosts.

 
Jörg H. Fritz (NPI) is Associate Professor in the Department of Microbiology and Immunology at McGill University and a member of the McGill Research Center on Complex Traits (MRCCT), a center dedicated to finding new targets for intervention in infectious and inflammatory diseases. His research led to the development of the novel vaccine adjuvant IC31 with Intercell AG/Valneva, currently in clinical trials. The research group of Dr. Fritz investigates cellular and molecular mechanisms of innate and adaptive immunity at mucosal surfaces. His research program puts a particular focus on understanding how innate immunity and antigen-specific T and B cell responses are shaped and regulated by innate lymphoid cells (ILC) during pulmonary and intestinal infectious or environmental challenges.

 
Ciriaco A. Piccirillo is a Professor in the Department of Microbiology and Immunology at McGill University, senior scientist at the Research Institute of the McGill University Health Centre (RI-MUHC), and a member of the McGill Research Center on Complex Traits (MRCCT). He leads an internationally recognized research program which focuses on the regulation of T cell responses mediated by Foxp3+ regulatory T cells in autoimmune, infectious and inflammatory diseases. His research is responsible for many seminal and pioneering studies on the biology and function of Foxp3+ regulatory T cells in a variety of animal models, non-human primates and humans. His current research program makes use of a variety of mouse models and in human subjects to monitor and characterize the development and functional dynamics of regulatory T cell function in lymphoid and non-lymphoid tissues in various inflammatory settings. His research program also focuses on the development of novel immunotherapeutic strategies to monitor and manipulate Foxp3+ regulatory T cells function and ultimately modulate immune responses in infectious, autoimmune and inflammatory disorders, cancers or immunodeficiencies.