Evaluation of IFN-γ response to rotavirus and non-structural protein NSP4 of rotavirus in children following severe rotavirus diarrhea

Abstract

Background Rotavirus (RV) is the commonest cause of severe gastroenteritis in young children worldwide. However the natural immune mechanisms controlling and preventing rotavirus disease in humans are not fully understood. Objective To examine cellular immune responses to whole rotavirus (vaccine strain, 116E) and non-structural protein-4 (116E-NSP4) in children during natural rotavirus-infection. Study design Gamma-interferon (IFN-γ) responses were evaluated by enzyme-linked immunospot assay in peripheral blood mononuclear cells from children with RV ( n = 26) or non-RV ( n = 10) gastroenteritis and from RV-exposed adults ( n = 10). Additionally, IL-4 responses were assessed in 5 of the 10 adults and 6 of 26 RV-infected children. Results IFN-γ secreting cells specific to whole RV were detected in 68% of RV-positive children and to NSP4 in 43% of these children between 4 and 30 days of illness onset. IFN-γ responses were transient and were found higher in RV-exposed adults than in children ( P < 0.05). Within the RV-positive group, IFN-γ responses in children with prior RV-exposure were higher than children without prior exposure ( P < 0.05). The response to whole RV and NSP4 were positively correlated ( P < 0.01, r s = 0.66). Conclusions Significant IFN-γ responses to rotavirus candidate vaccine strain 116E were detected in children during natural RV-infection and in RV-exposed adults. Significant IFN-γ responses to NSP4 were also observed in these study groups.