Co-evolutionary dynamics of viral pathogens and human antibody response

forthcoming

Vertebrates, like ourselves, use adaptive immune cells to protect themselves from pathogens. Predicting mutations of these pathogens, together with the immune response, is essential for the design of vaccines and therapies. CoEvolve will map the co-evolution of immune repertoires and viral populations, to forecast likely properties of future infecting strains and to design interventions that improve immune control. Much effort has been devoted to evolving viral pathogens, but most studies focus either on viral evolution or on immune adaptation in individual hosts. Yet pathogen and host dynamics are coupled: viruses escape from immune recognition, while immune systems adapt to changing viruses. CoEvolve takes an integrative approach: we will study host immune evolution and viral evolution together and on equal footing. We will focus on two viruses, influenza and SARS-CoV-2, that cause severe respiratory diseases. Both viruses evolve rapidly and are transmitted between hosts in acute infections. Influenza has evolved in humans over decades, while SARS-CoV-2 has entered humans more recently and is likely reaching a long-term co-evolutionary state. In both systems, we will track and predict co-evolution on multiple scales: in laboratory experiments, longitudinal human tracking studies, and globally circulating populations. CoEvolve will develop new molecular binding and neutralisation assays for high-throughput tracking of host-pathogen immune interactions and multi-scale inference methods for coevolution. Based on these data and methods, we will • map co-evolutionary landscapes of viral-immune molecular interactions, • build data-driven models of human immunity and co-evolutionary dynamics, • predict viral-immune co-evolution and inform vaccination strategies to optimize immune control. CoEvolve addresses a fundamental science problem, to understand host-pathogen co-evolution from its molecular basis, and will break ground towards improved public health interventions.