%0 Journal Article
%T T cell hybrid immunity against SARS-CoV-2 in children: a longitudinal study.
%A Qui M
%A Hariharaputran S
%A Hang SK
%A Zhang J
%A Tan CW
%A Chong CY
%A Low J
%A Wang L
%A Bertoletti A
%A Yung CF
%A Le Bert N
%J EBioMedicine
%V 105
%N 0
%D 2024 Jul 18
%M 38896919
%F 11.205
%R 10.1016/j.ebiom.2024.105203
%X <B>BACKGROUND: </B>Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children.<BR><B>METHODS: </B>We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining.<BR><B>RESULTS: </B>After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens.<BR><B>CONCLUSIONS: </B>Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19.<BR><B>BACKGROUND: </B>This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).