RESEARCH ARTICLE Antigenic Relatedness of Norovirus GII.4 Variants Determined by Human Challenge

The GII.4 noroviruses (NoVs) are a single genotype that is responsible for over 50 % of NoV gastroenteritis epidemics worldwide. However, GII.4 NoVs have been found to undergo an-tigenic drifts, likely selected by host herd immunity, which raises an issue for vaccine strate-gies against NoVs. We previously characterized GII.4 NoV antigenic variations and found significant levels of antigenic relatedness among different GII.4 variants. Further characteri-zation of the genetic and antigenic relatedness of recent GII.4 variants (2008b and 2010 cluster) was performed in this study. The amino acid sequences of the receptor binding in-terfaces were highly conserved among all GII.4 variants from the past two decades. Using serum samples from patients enrolled in a GII.4 virus challenge study, significant cross-re-activity between major GII.4 variants from 1998 to 2012 was observed using enzyme-linked immunosorbent assays and HBGA receptor blocking assays. The overall abilities of GII.4 NoVs to bind to the A/B/H HBGAs were maintained while their binding affinities to individual ABH antigens varied. These results highlight the importance of human HBGAs in NoV evo-lution and how conserved antigenic types impact vaccine development against GII.4 variants