Why do Norovirus pandemics occur and how can we control them? (360G-Wellcome-203268_Z_16_Z)

Noroviruses cause annual epidemics of gastrointestinal infection resulting in significant ill-health and disruption to health services. Frequent genetic mutation causing drift of epidemic strains and recombination leads to worldwide spread of pandemic strains. Approximately 3 million cases/annum occur in the UK with health-care costs exceeding £100M1. The advent of new vaccines against two genotypes is encouraging. However, ignorance about the drivers of norovirus strain evolution and spread is a barrier to effective vaccine design and deployment. This multidisciplinary consortium will investigate, through integrated studies, host and pathogen factors that lead to epidemic and pandemic norovirus spread and affect disease severity. Our international team has expertise in norovirus genome sequencing, phylogenetic analysis, norovirus antigen mapping, public health epidemiology and mathematical modelling. We will make use of existing clinical and public health datasets and samples, and an ongoing community study of norovirus burden to answer questions about transmission and carriage. Norovirus genome sequencing and phylogeography, in the context of international sequence-databases and antigenic mapping of sera will elucidate the origins and evolution of pandemic strains and outbreaks. Mathematical models, developed and fitted to the available data will provide novel insights into norovirus pathogenesis and transmission, informing vaccine design and immunisation strategies.