Peering into the future of SARS-CoV-2 evolution through the prism of host-pathogen co-evolution
2Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Israel
3Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Israel
4Vaccine and Infectious Disease Division, Fred Hutch Cancer Research Center, USA
Viruses evolve in response to immune pressure, as demonstrated by the ongoing SARS-CoV-2 pandemic.The rapid evolution of SARS-CoV-2 has led to the rise of novel variants of concern that have a variety of mutations that have been demonstrated to be involved in immune escape from both antibodies and T-cells. This has also led to the recent introduction of bi-valent vaccines and highlighted the importance of developing universal SARS-CoV-2 vaccines. The abundance of virological and immunological data on SARS-CoV-2 provides a unique opportunity to develop novel immunoinformatic tools for characterizing the mutational landscape of the virus through the prism of the host immune system. We have been developing methods for quantifying the immune escape potential of viral mutations considering both antibodies and T-cells. These methods leverage the viral sequence databases, structures of antibody-spike complexes, T-cell epitopes, and data on functional T-cell and antibody responses, and were optimized using information about previously characterized immune-escape mutations. These computational tools can then be used to predict the effect of future mutations on immune escape, in order to identify combinations of mutations which may have improved immune-escape properties, and may appear in future variants of concern. These tools may serve as an important building block in the development of universal SARS-CoV-2 vaccines.