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

Hensen,Lobke C.M.
Streng,Bianca M.M.
van Wijk,Femke
Nierkens,Stefan
van Binnendijk,R.S.
Buisman,Anne-Marie
Coppus,Antonia M.W.
Geurts van Kessel,Corine H.
de Graaf,Gert
Van Der Klis,Fiona R.
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Abstract
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.
Description
Projectcode: 4200P068 (42003202)
Date
2025
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Research Projects
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Keywords
Down syndrome, COVID-19, SARS-CoV-2, mRNA and vector vaccines, T cells, IFNy, SDG 3 - Good Health and Well-being
Citation
Hensen, L C M, Streng, B M M, van Wijk, F, Nierkens, S, van Binnendijk, R S, Buisman, A-M, Coppus, A M W, Geurts van Kessel, C H, de Graaf, G, Van Der Klis, F R, Lamberts, R, Vidarsson, G, Ruckwardt, T J, de Vries, E, de Vries, R D, Weijerman, M E, Weinberger, D M, Wildenbeest, J G, Bont, L J & Delemarre, E M 2025, 'T-cell responses to SARS-CoV-2 vaccinations in adults with Down syndrome : A prospective cohort study', Human Vaccines & Immunotherapeutics, vol. 21, no. 1, e2583416. https://doi.org/10.1080/21645515.2025.2583416
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