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Hum Vaccin Immunother . T-cell responses to SARS-CoV-2 vaccinations in adults with Down syndrome - a prospective cohort study

tetano

Editor, Senior Moderator
Hum Vaccin Immunother


. 2025 Dec;21(1):2583416.
doi: 10.1080/21645515.2025.2583416. Epub 2025 Nov 6. T-cell responses to SARS-CoV-2 vaccinations in adults with Down syndrome - a prospective cohort study

Lobke C M Hensen[SUP] 1 2 [/SUP], Bianca M M Streng[SUP] 1 [/SUP], Femke van Wijk[SUP] 2 [/SUP], Stefan Nierkens[SUP] 2 3 [/SUP], Rob S van Binnendijk[SUP] 4 [/SUP], Anne-Marie Buisman[SUP] 4 [/SUP], Antonia M W Coppus[SUP] 5 [/SUP], Corine H Geurts van Kessel[SUP] 6 [/SUP], Gert de Graaf[SUP] 7 [/SUP], Fiona R van der Klis[SUP] 4 [/SUP], Regina Lamberts[SUP] 7 [/SUP], Gestur Vidarsson[SUP] 8 9 [/SUP], Tracy J Ruckwardt[SUP] 10 [/SUP], Esther de Vries[SUP] 11 12 [/SUP], Rory D de Vries[SUP] 6 [/SUP], Michel E Weijerman[SUP] 13 [/SUP], Daniel M Weinberger[SUP] 14 [/SUP], Joanne G Wildenbeest[SUP] 1 [/SUP], Louis J Bont[SUP] 1 [/SUP], Eveline M Delemarre[SUP] 1 2 [/SUP]



Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.

Keywords: COVID-19; Down syndrome; IFNγ; SARS-CoV-2; T cells; mRNA and vector vaccines.

 
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