T-cell responses to primary SARS-CoV-2 vaccination in Down syndrome–From childhood to adulthood

Down syndrome (DS) is the most common genetic disorder worldwide and associated with high morbidity and mortality rates during the COVID-19 pandemic. For safety reasons, SARS-CoV-2 vaccine schedules and dosages were age-dependent, with children <12 years (y) receiving a lower dose than adolescents and adults. While we previously reported age-dependent antibody responses after SARS-CoV-2 vaccination in children with DS, cellular vaccine responses in this population remain insufficiently characterized. We evaluated vaccine-induced T-cell responses in children with DS following primary mRNA SARS-CoV-2 vaccination. We measured SARS-CoV-2-specific T-cell abundance (N = 40) and their interferon-gamma (IFNγ) production (N = 55) after spike antigen re-stimulation in participants aged 3–74 y. We found no significant difference in the re-activation of SARS-CoV-2-specific CD4⁺ T cells between adolescents (12–17 y) and adults. Children aged 5–11 y exhibited significantly lower re-activation of CD4⁺ T cells compared with adolescents. IFNγ production was similar across all age groups. Besides previously reported age-dependent antibody responses, these findings suggest that reduced dosing may also be associated with diminished T-cell re-activation in children with DS. Therefore, these children aged 5–11 y may benefit from receiving a booster or vaccine doses similar to those of older age groups to ensure optimal immunity and protection. Clinical trial registration: NCT05145348.