T-cell responses to SARS-CoV-2 vaccinations in adults with Down syndrome – a prospective cohort study

Down syndrome (DS) is associated with immune dysfunction, which led to higher hospitalization and mortality rates during the COVID-19 pandemic. We previously showed that antibody concentrations were lower in adults with DS after primary SARS-CoV-2 vaccination. However, knowledge on cellular vaccine-induced responses in DS is limited. Here, we investigated the T-cell response induced by SARS-CoV-2 vaccination in adults with DS. We included adults with DS and healthy controls (HC) between 18 and 64 years following primary (mRNA and vector) and booster (mRNA) SARS-CoV-2 vaccination. Using flow cytometry, SARS-CoV-2-specific T cells were analyzed after spike peptide re-stimulation. Additionally, interferon-gamma (IFNγ) production by SARS-CoV-2-specific T cells was measured with an IFNγ release assay (IGRA) after antigen stimulation. We observed major deficits in naive CD4⁺ and CD8⁺ T cells in adults with DS as previously described. However, overall there was no difference in the percentage of SARS-CoV-2-specific T cells or IFNγ production by these cells after primary vaccination, albeit with vaccine-specific differences. IFNγ concentrations measured by IGRA after primary vaccination were comparable between DS and HC. Booster vaccination increased SARS-CoV-2-specific T cells in HC but not in DS, while IFNγ release (IGRA) increased to similar concentrations. In conclusion, we show that while functional T-cell responses (IFNγ production) are comparable after primary and booster vaccination, the magnitude (percentage of SARS-CoV-2-specific T cells) may be lower after mRNA vaccination. We previously showed lower antibody concentrations and profound abnormalities in the naive T-cell compartment, warranting further investigation into T-cell-B-cell-interactions after vaccination in adults with DS.<b>Clinical trial registration</b>: NCT05145348 https://www.clinicaltrials.gov/study/NCT05145348?locStr=Netherlands&country=Netherlands&cond=Down%20Syndrome&term=SARS-CoV-2%20Vaccination&rank=1.<b>Start date</b>: 2021-02-03.