Human norovirus cultivation models, immune response and vaccine landscape

Norovirus infections are a leading cause of gastroenteritis worldwide. Despite the substantial global health burden and economic impact, there are currently no approved antiviral therapeutics or vaccines. Additionally, much of our knowledge of norovirus comes from experiments using surrogate viruses, such as murine norovirus and feline calicivirus. The challenge surrounding human norovirus research arises from a lack of robust cell culture systems and efficient animal models. In this review, we explore recent advances in the in vitro cultivation of human norovirus and reverse genetics systems and discuss commonly used in vivo models. We summarize the current understanding of both innate and adaptive immune responses to norovirus infection and provide an overview of vaccine strategies and the current clinical trial landscape, with a focus on the only vaccine candidate that has reached phase III clinical development stage.