Variable and conserved B cell epitopes of GII.4 human noroviruses

Norovirus is a leading cause of acute gastroenteritis worldwide, imposing a major burden on public health and healthcare systems. Despite its significant medical impact, no licensed vaccines or specific antiviral therapies are currently available. Norovirus vaccine development is complicated by several factors, including the extreme genetic and antigenic diversity. In particular, the predominant genotype GII.4 exhibits a continuous emergence of novel variants that can evade immune responses acquired from previous infections. In this manuscript, we will summarize the characteristics and current knowledge of the B cell responses elicited by conserved and variable GII.4 epitopes and discuss how these findings inform our understanding of responses to other pandemic norovirus genotypes. We also highlight how ongoing research in this area may provide critical insights for the development of broadly protective norovirus vaccines.