Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup...

Majority of norovirus (NoV) outbreaks and sporadic infections in the past 20 years have been caused by GII.4 variants. In 2014, NoV GII.17 genotype replaced GII.4 strains in several Asian countries and major outbreaks were reported in other continents. As GII.17 is a recently evolved NoV strain, there is a gap especially in immunogenicity data. In this study, we investigated GII.17 virus-like particle (VLP) binding to various cellular ligands, histo-blood group antigens (HBGAs), using human saliva, pig gastric mucin, and synthetic oligosaccharides as HBGA sources. The level of GII.17 immunological cross-reactivity was determined in mice immunized with different monovalent and multivalent NoV VLP compositions. Furthermore, healthy adult volunteers with natural NoV exposure history were analyzed for GII.17-specific seroresponses. The results showed that GII.17 Kawasaki VLPs bind to a wide range of HBGAs, even though fewer than GII.4 VLPs. Immunization of mice with a multivalent VLP formulation containing different genogroup II NoV VLPs was required to obtain the highest magnitude of cross-reactive binding antibodies to GII.17. However, coimmunization with different VLP genotypes did not improve potentially neutralizing antibodies to GII.17, which remained very moderate. Low pre-existing cross-reactive antibodies to GII.17 observed in human adults indicate the presence of a large pool of susceptible individuals in this population. These data suggest that GII.17 and alike newly emerging distinct NoV genotypes should be considered as an antigenic component for vaccine formulations, which currently widely rely on GII.4-specific immunity.