TY - JOUR
T1 - T-cell responses to SARS-CoV-2 vaccinations in adults with Down syndrome–a prospective cohort study
AU - Hensen, Lobke C.M.
AU - Streng, Bianca M.M.
AU - van Wijk, Femke
AU - Nierkens, Stefan
AU - van Binnendijk, Rob S.
AU - Buisman, Anne Marie
AU - Coppus, Antonia M.W.
AU - Geurts van Kessel, Corine H.
AU - de Graaf, Gert
AU - van der Klis, Fiona R.
AU - Lamberts, Regina
AU - Vidarsson, Gestur
AU - Ruckwardt, Tracy J.
AU - de Vries, Esther
AU - de Vries, Rory D.
AU - Weijerman, Michel E.
AU - Weinberger, Daniel M.
AU - Wildenbeest, Joanne G.
AU - Bont, Louis J.
AU - Delemarre, Eveline M.
N1 - Publisher Copyright:
© 2025 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2025/12
Y1 - 2025/12
N2 - 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. Clinical trial registration: NCT05145348 https://www.clinicaltrials.gov/study/NCT05145348?locStr=Netherlands&country=Netherlands&cond=Down%20Syndrome&term=SARS-CoV-2%20Vaccination&rank=1. Start date: 2021–02-03.
AB - 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. Clinical trial registration: NCT05145348 https://www.clinicaltrials.gov/study/NCT05145348?locStr=Netherlands&country=Netherlands&cond=Down%20Syndrome&term=SARS-CoV-2%20Vaccination&rank=1. Start date: 2021–02-03.
KW - COVID-19
KW - Down syndrome
KW - IFNγ
KW - mRNA and vector vaccines
KW - SARS-CoV-2
KW - T cells
UR - https://www.scopus.com/pages/publications/105020992947
U2 - 10.1080/21645515.2025.2583416
DO - 10.1080/21645515.2025.2583416
M3 - Article
C2 - 41196011
AN - SCOPUS:105020992947
SN - 2164-5515
VL - 21
JO - Human Vaccines and Immunotherapeutics
JF - Human Vaccines and Immunotherapeutics
IS - 1
M1 - 2583416
ER -
