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| Name | Class |
|---|---|
| ZonMw: The Netherlands Organisation for Health Research and Development | OTHER |
| National Institute for Public Health and the Environment (RIVM) | OTHER_GOV |
| Stichting Downsyndroom (SDS) | UNKNOWN |
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The risk of severe course of SARS-CoV-2 infection in people with Down Syndrome is substantially increased. The risk of death is 3-10 fold higher than in healthy people. SARS-CoV-2 vaccines have been registered for adults and adolescents but none of them have been studied in people with Down Syndrome. Vaccine responses in people with Down Syndrome are known to be suboptimal. Therefor the objective of this study is to assess the immunogenicity of SARS-CoV-2 vaccination in people with Down syndrome.
To do so, the antibody response, cellulair and mucosal immuneresponse in people with Down syndrome after the SARS-CoV-2 vaccination will be evaluated and compared to healthy controls.
All participants will receive two vaccinations against COVID-19 according to the manufacturer's instructions as part of the Dutch SARS-CoV-2 vaccination program (GGD/RIVM). To assess the immune response after vaccination, blood samples will be collected at baseline (i.e. <2 months prior to first vaccination (t=1)), 21-28 days after first vaccination and prior to second vaccination (t=2), 28 days (3-6 weeks) (t=3) and 12 (+/- 1) months (t=4) after the second vaccination. To evaluate haematological parameters, additional blood samples will be collected at baseline, 21-28 days after the first vaccination and 28 days after the second vaccination. Per visit/time-point maximum 60 ml blood will be drawn. In children the maximum amount of blood taken per visit/time-point will be 0,8 ml/kg up to 60 ml. In addition Mucosal Lining Fluid (MLF) samples will be collected at 28 days (3-6 weeks) (t=3) and 12 (+/- 1) months (t=4) after the second vaccination to evaluate the mucosal immune response after SARS-CoV-2 vaccination. In the pediatric part of the study Mucosal Lining Fluid (MLF) samples will be collected at all timepoints.
Although vaccine administration is not part of this study, vaccine type, batch number and dosing will be registered. This information will be obtained from the "COVID-vaccination information and monitoring system (CIMS)" of the RIVM.
Clinical course including the occurrence of COVID-19 will be monitored during the first year after vaccination. To evaluate vaccination related AEs, patients will be asked to collect solicited local and systemic AEs for 7 days after each vaccination using an online questionnaire, as vaccination related AEs are mainly expected in the first week after vaccination. The link to the online questionnaires will be sent to the emailaddress of the participants and/or their representative/carer. If the participants and/or their representative/carers are not able to fill out the diary online, they will be contacted by phone.
Although this study is not powered to detect differences in protection against COVID-19 between patients and controls, information on incidence of SARS-CoV-2 infection, outcome of COVID-19 will be collected up to 12 months after vaccination for descriptive purposes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Down syndrome, adults | Adults and adolescents with Down syndrome >16 years old. |
| |
| Healthy control, adults | Healthy adults and adolescents without Down syndrome > 16 years old. Without any significant comorbidities. |
| |
| Down syndrome, children | Children with Down syndrome < 16 years old. |
| |
| Healthy control, children | Healthy children without Down syndrome < 16 years old. Without any significant comorbidities. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca) | Biological | The vaccination is not part of the study, but part of the national immunization programme of the Netherlands. Blood will be drawn at 4 time points: baseline (t=1, <2 months prior to first vaccination); t=2: 21-28 days after first vaccination and prior to second vaccination; t=3: 28 (21-42) days after second vaccination; t=4: 12 months (+/- 1 month) after second vaccination. Mucosal Lining Fluid (MLF) samples will be collected at 28 days (3-6 weeks) (t=3) and 12 (+/- 1) months (t=4) after the second vaccination. |
| Measure | Description | Time Frame |
|---|---|---|
| Antibody based immune response to vaccination against COVID-19 28 days (t=3) after the second vaccination as compared to controls. | Participants will be classified as responders or non-responders. The definition of response will be based on the latest available data from the pivotal studies and will be defined prior to data analyses and the first database lock. The percentage of responders in the DS cohort will be compared with the percentage responders in the HS cohort. | 28 days after the second vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| Longevity of SARS-CoV-2 specific antibodies | Longevity of SARS-CoV-2 specific antibodies after the second vaccination will be compared between cohorts. | 1 year after the second vaccination |
| SARS-CoV2 specific T cell response |
| Measure | Description | Time Frame |
|---|---|---|
| Determination of fucosylation, sialylation, galactosylation and bisection of IgG in patients with a history of COVID-19. | Determination of levels of fucosylation, sialylation, galactosylation and bisection of both bulk IgG and anti-SARS-CoV-2 S protein IgG in participants with a history of proven mild or severe COVID-19. | All time points |
Inclusion Criteria:
Exclusion Criteria:
Down syndrome cohort:
Healthy control cohort:
- As in Down Syndrome cohort
Plus:
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Down syndrome:
The patient population will either live in institutions or outside these facilitys depending on the cognitive functions and additional care needed. Children will mostly live with their parents. All participants will live in the Netherlands
Healthy control:
All healthy control participants will live in the Netherlands, no specific region.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joanne G Wildenbeest, MD, PhD | Contact | 0031887563776 | J.G.Wildenbeest-2@umcutrecht.nl | |
| Bianca MM Streng, MD | Contact | +31650177982 | b.m.m.streng-3@umcutrecht.nl |
| Name | Affiliation | Role |
|---|---|---|
| Louis J Bont, MD, PhD | UMC Utrecht | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UMC utrecht | Recruiting | Utrecht | 3584 CX | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42223472 | Derived | Hensen LCM, Streng BMM, van Wijk F, Nierkens S, Wildenbeest JG, Bont LJ, Delemarre EM; PRIDE study group. T-cell responses to primary SARS-CoV-2 vaccination in Down syndrome - From childhood to adulthood. Hum Vaccin Immunother. 2026 Dec 31;22(1):2670839. doi: 10.1080/21645515.2026.2670839. Epub 2026 Jun 1. | |
| 41447779 | Derived |
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| Sanquin Research & Blood Bank Divisions | OTHER |
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Serum, Whole blood, PBMC's, mucosal nose swab
|
The number of IFN-ɣ producing SARS-CoV2 specific T cells/million PBMC (mean of 3 measures)
| Number of T cells will be measured at baseline, at 21-28 days after the first vaccination and at 28 days after the second vaccination |
| Mucosal SARS-CoV-2 specific antibodies | Antibody titers will be compared between cohorts and with antibody titers in blood | Mucosal antibodies will be measured 28 days and 12 months after the second vaccination. |
| Age-specific T-cell immunophenotyping |
Immunophenotyping, in particular naïve T-cell counts will be measured. |
| All time points |
| Neutralizing capacity of SARS-CoV-2 antibodies | Comparison of the neutralizing capacity of SARS-CoV-2 antibodies between cohorts | Measurements at baseline, 21-28 days after first vaccination and 28 days, and 12 months after second vaccination. |
| Incidence and outcome of SARS-CoV-2 infection | Incidence and outcome during period of 12 months after vaccination. For participants with a positive test, information about disease severity will be presented including hospital admissions, use of oxygen, intensive care admission and mechanical ventilation | During time period of 12 months after vaccination. |
| Streng BMM, Hensen LCM, Delemarre EM, Binnendijk RS, Smits G, den Hartog G, van der Klis FR, de Vries E, Burger JA, van Gils MJ, Coppus AMW, Weijerman ME, Lamberts R, de Graaf G, Bont LJ, Wildenbeest JG. Antibody concentration and function following SARS-CoV-2 vaccination decrease with age in adults and children with Down syndrome. Vaccine. 2026 Feb 15;73:128079. doi: 10.1016/j.vaccine.2025.128079. Epub 2025 Dec 24. |
| 41196011 | Derived | Hensen LCM, Streng BMM, van Wijk F, Nierkens S, van Binnendijk RS, Buisman AM, Coppus AMW, Geurts van Kessel CH, de Graaf G, van der Klis FR, Lamberts R, Vidarsson G, Ruckwardt TJ, de Vries E, de Vries RD, Weijerman ME, Weinberger DM, Wildenbeest JG, Bont LJ, Delemarre EM. T-cell responses to SARS-CoV-2 vaccinations in adults with Down syndrome - a prospective cohort study. Hum Vaccin Immunother. 2025 Dec;21(1):2583416. doi: 10.1080/21645515.2025.2583416. Epub 2025 Nov 6. |
| 35748853 | Derived | Streng BMM, Bont M, Delemarre EM, Binnendijk RS, Smit G, den Hartog G, Coppus AMW, de Vries E, Weijerman ME, Lamberts R, de Graaf G, van der Klis FR, Vidarsson G, Rave N, Bont LJ, Wildenbeest JG. Decreased Antibody Response After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Patients With Down Syndrome. J Infect Dis. 2022 Sep 4;226(4):673-677. doi: 10.1093/infdis/jiac235. |
| ID | Term |
|---|---|
| D004314 | Down Syndrome |
| ID | Term |
|---|---|
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D025063 | Chromosome Disorders |
| D030342 | Genetic Diseases, Inborn |
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| ID | Term |
|---|---|
| D000090982 | BNT162 Vaccine |
| D000090985 | ChAdOx1 nCoV-19 |
| ID | Term |
|---|---|
| D000087503 | mRNA Vaccines |
| D000087504 | Nucleic Acid-Based Vaccines |
| D014614 | Vaccines, Synthetic |
| D011994 | Recombinant Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D000086663 | COVID-19 Vaccines |
| D014765 | Viral Vaccines |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D019444 | Vaccines, DNA |
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