Prospective Monitoring of Antibody Response Following COVID-19 Vaccination in Patients With Down Syndrome. (PRIDE)

Prospective Monitoring of Antibody Response Following COVID-19 Vaccination in Patients With Down Syndrome

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.

Study Overview

• Status: Recruiting
• Conditions: Down Syndrome; SARS-CoV-2 Vaccination
• Intervention / Treatment: Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 640

Contacts and Locations

• Study Contact: Name: Joanne G Wildenbeest, MD, PhD; Phone Number: 0031887563776; Email: J.G.Wildenbeest-2@umcutrecht.nl
• Study Contact Backup: Name: Bianca MM Streng, MD; Phone Number: +31650177982; Email: b.m.m.streng-3@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • UMC Utrecht
    • Contact: Bianca MM Streng, MD; Phone Number: +31650177982; Email: b.m.m.streng-3@umcutrecht.nl
    • Contact: Joanne G Wildenbeest, MD, PhD; Email: J.G.Wildenbeest-2@umcutrecht.nl
    • Principal Investigator: Louis J Bont, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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.

Description

Inclusion Criteria:

• Willing to receive routine COVID-19 vaccination with Pfizer, Moderna or AstraZeneca vaccine.
• Age: ≥12 years or < 12 years once vaccine is recommended for routine use in the respective age group
• Either Down syndrome (DS) or household contacts without DS of participant with DS.

Exclusion Criteria:

Down syndrome cohort:

• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention(s).
• Organ transplant recipients
• Active malignancy or completion of treatment for malignancy in previous 3 months
• Infection with Human Immunodeficiency Virus (HIV)
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

Healthy control cohort:

- As in Down Syndrome cohort

Plus:

• Active medical care for inherited or acquired immune deficiency
• Any severe comorbidity for which regular medical care is needed (e.g. heart failure, COPD, diabetes)

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Down syndrome, adults; Adults and adolescents with Down syndrome >16 years old.	Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca); 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.
Healthy control, adults; Healthy adults and adolescents without Down syndrome > 16 years old. Without any significant comorbidities.	Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca); 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.
Down syndrome, children; Children with Down syndrome < 16 years old.	Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca); 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.
Healthy control, children; Healthy children without Down syndrome < 16 years old. Without any significant comorbidities.	Biological: Immune response to Sars-CoV-2 vaccinations; including COVID-19 vaccin Moderna, Comirnaty (Pfizer) and Vaxzevria (AstraZeneca); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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.

Other Outcome Measures

Outcome Measure	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
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.

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Sanquin Research & Blood Bank Divisions; National Institute for Public Health and the Environment (RIVM); ZonMw: The Netherlands Organisation for Health Research and Development; Stichting Downsyndroom (SDS)
• Investigators: Principal Investigator: Louis J Bont, MD, PhD, UMC Utrecht

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: December 3, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Actual): December 30, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Down Syndrome; SARS-CoV-2 vaccination; Immuneresponse
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Down Syndrome
• Other Study ID Numbers: NL76336.041.21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No