Profiling of humoral immune responses to norovirus in children across Europe

AbstractHuman noroviruses are a major cause of gastroenteritis outbreaks worldwide. The majority of outbreaks and sporadic cases are caused by norovirus genotype GII.4 but 48 capsid genotypes and 60 polymerase genotypes (P-types) have been described, some of which are frequently reported while others are rarely detected. Little is known about the circulation and reservoirs of the less common genotypes. In this study, we have investigated whether children could pose a possible reservoir for undetected circulation of norovirus diversity. We, therefore, tested IgG and IgA responses of sera obtained from 287 children aged <1-month to 5.5-years on a protein microarray against P particles representing 30 norovirus GI and GII genotypes. We further profiled immune responses against the P-type by assessing antigenicity and seroprevalence of the non-structural proteins. The overall seroprevalence was 95.3% in children up to six months old (maternal antibodies), followed by a decrease to 59.6% up to 12 months, and an increase to 84.7% by the age of 5.5 years. We detected antibody responses against all tested genotypes, with the most specific IgG and IgA responses directed against the GII.2, GII.3, GII.4, and GII.6 capsid genotypes, which are the most frequently reported noroviruses in outbreaks. We also detected antibodies against the non-structural proteins p48 and p22 in sera of older children, predominantly against GII genotypes.While we found no evidence to suggest that rarely detected genotypes widely circulate in children, this is the first study to investigate seroprevalence against such a wide variety of human norovirus capsid and polymerase genotypes.ImportanceNorovirus is a leading cause of epidemic acute gastroenteritis, causing severe disease in children, the elderly, and immunocompromised individuals. Although norovirus is a diverse genus of viruses, the majority of reported cases are caused by viruses of the GII.4 genotype. Many of the genotypes are rarely detected and it is unknown where they circulate between outbreaks. Here we investigated the possibility of children posing a reservoir for undetected circulation. While previous serological studies have tested antibodies against a limited set of capsid genotypes, we profiled the antibody repertoire of children against the capsid and the non-structural proteins, representing the known diversity of human noroviruses. While we detected high seroprevalence in children older than one year, we found no evidence to suggest a wide circulation of rare genotypes in children in Europe.