Down syndrome is associated with immune dysregulation and in line with previous studies, we observed lower naive CD4+ and CD8+ T cells, B-cell lymphopenia and lower CD4+ RTE within DS participants of the PRIDE study.4–6,21 Nonetheless, these differences do not seem to impact the vaccine specific response on a cellular level, as we observed similar percentages of SARS-CoV-2-specific CD4+ T cells in DS and HC after primary vaccination (mRNA and vector combined) and after an mRNA-based booster vaccination. Here, CD4 is linked to Down syndrome.