Abstract
Most of the research effort to understand protective immunity against norovirus (NoV) has focused on humoral immunity, whereas immunity against another major pediatric enteric virus, rotavirus (RV), has been studied more thoroughly. The aim of this study was to investigate development of cell-mediated immunity to NoV in early childhood. Immune responses to NoV GI.3 and GII.4 virus-like particles and RV VP6 were determined in longitudinal blood samples of 10 healthy children from three months to four years of age. Serum IgG antibodies were measured using enzyme-linked immunosorbent assay and production of interferon-gamma by peripheral blood T cells was analyzed by enzyme-linked immunospot assay. NoV-specific T cells were detected in eight of 10 children by the age of four, with some individual variation. T cell responses to NoV GII.4 were higher than those to GI.3, but these responses were generally lower than responses to RV VP6. In contrast to NoV-specific antibodies, T cell responses were transient in nature. No correlation between cell-mediated and antibody responses was observed. NoV exposure induces vigorous T cell responses in children under five years of age, similar to RV. A role of T cells in protection from NoV infection in early childhood warrants further investigation.
Highlights
Noroviruses (NoVs) and rotaviruses (RVs) are leading causes of severe acute gastroenteritis (AGE) in children under five years of age[1]
During the study period all children seroconverted to NoV, either to genogroup I (GI).[3] or genogroup II (GII).[4] or both, while eight of 10 subjects seroconverted to RV VP6 (Tables 1–3)
Lowest levels of NoV (Fig. 1a,b) and RV (Fig. 1c) –specific antibodies were observed at the age of 6 or 12 months following the decrease of maternal antibodies, but the age of observed seroconversion varied from 1 to 4 years of age (Table 3)
Summary
Noroviruses (NoVs) and rotaviruses (RVs) are leading causes of severe acute gastroenteritis (AGE) in children under five years of age[1]. Unlike RV, NoV research lacks efficient cell culture system for virus propagation and thereby most immunological assays, such as surrogate neutralization assay as well as vaccine development, rely on antigenically and morphologically equivalent NoV VLPs11. Antigenic heterogeneity is a major issue in NoV protection, contributing to the lack of cross-protection between genogroup I (GI) and genogroup II (GII) NoVs and limited immunity between heterogenous strains within these genogroups[14,15,16]. NoVs and RVs2,20 use polymorphic set of histo-blood group antigen (HBGA) molecules expressed on gut epithelium as cell attachment factors/receptors in strain-specific manner[21]. Www.nature.com/scientificreports data supporting the protective role of IgA24,25, neutralizing antibodies[26] and T cells[27,28,29,30,31] is exhaustive. There is still much controversy and debate over the protective effect of these immunological components[24,32]
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