Paediatrics (RCH) - Research Publications
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ItemHisto-blood Group Antigen status of Australian Aboriginal children and seropositivity following oral rotavirus vaccination( 2022)Background: High rates of breakthrough rotavirus gastroenteritis have been reported among Aboriginal children living in rural and remote Australia despite receipt of two doses of oral rotavirus vaccine. Histo-blood group antigens (HBGAs) may mediate rotavirus genotype-dependent differences in susceptibility to rotavirus infection and immune responses to rotavirus vaccination. Methods: HBGA phenotype – Lewis and secretor status - was determined by enzyme immunoassay of saliva samples obtained from Australian Aboriginal children who were enrolled at age 6 to <12 months in a randomised clinical trial of an additional (booster) dose of oral rotavirus vaccine. Participants had received the routine two-dose schedule of oral rotavirus vaccine administered at age 6 weeks and 4 months. Non-secretor phenotype was confirmed by DNA extraction to identify FUT2 ‘G428A’ mutation. Rotavirus seropositivity was defined as serum anti-rotavirus IgA ≥ 20 AU/mL measured by ELISA on enrolment. Results: Of 156 children, 119 (76%) were secretors, 129 (83%) were Lewis antigen positive, and 105 (67%) were rotavirus IgA seropositive. Eighty-seven of 119 (73%) secretors were rotavirus seropositive, versus 4/9 (44%) weak secretors and 13/27 (48%) non-secretors. Eighty-nine of 129 (69%) Lewis antigen positive children were rotavirus seropositive versus 10 of 19 (53%) of those who were Lewis antigen negative. Conclusions Most Australian Aboriginal children were secretor and Lewis antigen positive. Non-secretor children were less likely to be seropositive for rotavirus following vaccination, but this phenotype was less common. HBGA status is unlikely to fully explain the underperformance of rotavirus vaccine at a population level among Australian Aboriginal children.
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ItemImmune Responses in an Infant with Congenital Heart Disease and Severe COVID-19( 2021)Children have lower hospitalisation and mortality rates for coronavirus disease-2019 (COVID-19) than adults; however, younger children (<4 years of age) 1 may develop more severe disease than older children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterized. We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19. Systemic cellular and cytokine profiling showed initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8+ T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4+T (but not CD8+T) cells occurred over time, with predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Significant in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory.
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ItemImmune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19( 2020)Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have mild or asymptomatic infection, but the underlying immunological differences remain unclear. We describe clinical features, virology, longitudinal cellular and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who were repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children were similar to their parents at all timepoints. All family members had salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincided with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child had IgG antibody detected against the S1 protein and virus neutralising activity ranging from just detectable to robust titers. Using a systems serology approach, we show that all family members demonstrated higher levels of SARS-CoV-2-specific antibody features than healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological evidence of infection. This raises the possibility that despite chronic exposure, immunity in children prevents establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may therefore not identify exposed children, with implications for epidemiological and clinical studies across the life-span.