Antigenic characterization of human noroviruses reveals limited cross-blocking between genotypes

Lauren Ford-Siltz, Food and Drug Administration

Lauren A Ford-Siltz, Joseph A Kendra, Kentaro Tohma, Michael Landivar, Kelsey A Pilewski, Yusra Gimie, Cara J Lepore, Yamei Gao, Gabriel I Parra Division of Viral Products, US Food and Drug Administration, Silver Spring, Maryland

Vaccines and immunity

Antibody responses to the norovirus major capsid protein are thought to be the primary contributor to immune protection. However, the vast genetic diversity presented by human noroviruses could challenge the development of effective protective responses. Studies have shown that humans can be infected with multiple norovirus genotypes throughout their lifetimes, yet reinfection patterns suggest some level of cross-protection among phylogenetically related genotypes. To experimentally determine the antigenic relationships between human norovirus genotypes, we immunized guinea pigs with virus-like particles (VLPs) representing most genotypes from Genogroups I and II and systematically performed carbohydrate blocking assays with all sera (n= 58) and a panel of VLPs (n= 30), which included viruses representing different variants within a genotype. Interestingly, through the process of determining assay conditions, we found that specific phylogenetically related genotypes (GII.1, GII.12, GII.2, GII.5, and GII.10) required glycochenodeoxychloic acid (GCDCA) to bind carbohydrate attachment factors; this requirement was dependent on the carbohydrate source. While cross-blocking was observed at the intra-genotype level and between certain genetically similar genotypes (GII.7, GII.8, GII.9, and GII.14), most genotypes were antigenically distinct. While intra-genotype blockade reactivity tolerated a genetic difference of ~10%, no apparent genetic distance was associated with cross-blockade at the inter-genotype level. Finally, we demonstrated that a multivalent vaccine, which included ten genotypes representing different phylogenetic clusters, was able to induce modest cross-protection against heterologous genotypes compared to monovalent vaccination. These data will set the baseline for studies that explore antigenic differences between norovirus genotypes and could facilitate the design of cross-protective vaccines.