Epitope D is a conformational epitope comprised of varying amino acids 393-395 and likely other nearby residues that are less clearly defined; however, additional mapping and crystallographic studies will be needed to clarify this epitope structure. With the emergence of the pandemic GII. 4 (Figure 4) . Previously, these residues have been implicated in regulating norovirus VLPcarbohydrate ligand binding interactions [13, 21, 43] . The identi-fication of Epitope D as a human antibody blockade epitope that changes over time provides direct support for our previous hypothesis that escape from protective herd immunity may drive changes in carbohydrate ligand binding affinities over time and potential retargeting of virus infection in different human populations [13, 40] .