Prospective monitoring of antibody response following COVID-19 vaccination in people with Down syndrome (PRIDE study)
Projectomschrijving
Het immuunsysteem bij volwassenen en kinderen met het Downsyndroom functioneert minder goed. Hierdoor lopen ze een hoger risico op complicaties bij een COVID-19-infectie. Voor hen is het dus belangrijk dat ze optimaal beschermd worden door vaccinatie. Er is nog niet onderzocht of het minder goed werken van het immuunsysteem ook invloed heeft op de werking van de vaccinaties tegen COVID-19. Dit onderzoek richt zich op het beoordelen van de immuunrespons en bijwerkingen bij mensen met het syndroom van Down na toediening van vaccinatie tegen COVID-19.
Doel
Het beoordelen van de immuunrespons en bijwerkingen na toediening van vaccinatie tegen COVID-19 bij volwassenen en kinderen met Downsyndroom.
Achtergrond
Mensen met Downsyndroom hebben een hoger risico om ernstig ziek te worden door het nieuwe coronavirus. Zij zullen daarom als een van de eersten gevaccineerd worden tegen het coronavirus. Eerder onderzoek laat zien dat vaccinaties minder goed werken bij mensen met Downsyndroom. Met de PRIDE studie wordt er onderzocht of het coronavaccin voldoende bescherming biedt aan volwassenen en kinderen met Downsyndroom.
Onderzoeksopzet
De immuunrespons wordt onderzocht door middel van bloedafnames en afname van neusslijm rondom de vaccinaties en een jaar na de tweede vaccinatie. De uitslagen zullen worden vergeleken met mensen zonder het syndroom van Down. Sinds eind juni mogen ook kinderen deelnemen aan de studie.
Eerste resultaten
Op 17 november 2021 verschenen de eerste resultaten van de PRIDE-studie. Uit het onderzoek blijkt dat volwassenen met Downsyndroom, na vaccinatie met Moderna of Pfizer, een lagere concentratie neutraliserende antistoffen hebben tegen COVID-19 dan mensen zonder downsyndroom. Na vaccinatie met AstraZeneca zijn er geen verschillen tussen de twee groepen. Het is nog wel de vraag wat deze resultaten precies zeggen over de bescherming tegen ziekte. Er is namelijk nog niet vastgesteld welke concentratie neutraliserende antistoffen daarvoor minimaal nodig is. Voor mensen met downsyndroom zijn gegevens over de cellulaire respons, die ook belangrijk is voor bescherming, nog niet beschikbaar.
Uitvoerende partijen
UMC Utrecht in samenwerking met de Stichting Down Syndroom.
Meer informatie
Prof.dr. L.J. Bont,
Dr. J.G. Wildenbeest
B.M.M. Streng
Emailadres: pride-onderzoek@umcutrecht.nl
Producten
Auteur: Bianca M M Streng, MD, Marin Bont, Eveline M Delemarre, MD/PhD, Rob S Binnendijk, PhD, Gaby Smit, Gerco den Hartog, PhD, Antonia M W Coppus, MD/PhD, Esther de Vries, MD/PhD, Michel E Weijerman, MD/PhD, Regina Lamberts, Gert de Graaf, PhD, Fiona R van der Klis, PhD, Gestur Vidarsson, PhD, Neele Rave, Louis J Bont, MD/PhD, Joanne G Wildenbeest, MD/PhD
Magazine: The journal of infectious diseases
Verslagen
Samenvatting van de aanvraag
BACKGROUND The risk of severe course of SARS-CoV-2 infection in people with Down Syndrome (DS) is substantially increased. The risk of death is 3-10 fold higher than in healthy people. COVID vaccines have been registered but none of them have been studied in people with DS. Vaccine responses in people with DS are suboptimal, probably related to the partial immune deficiency in DS characterized by – among other things - a lack of naïve T-cells. In this study (PRIDE), we aim to assess the immunogenicity of SARS-CoV-2 vaccination in patients with DS. OBJECTIVES Primary objective: to assess the antibody response after mRNA SARS-CoV-2 vaccination in people with Down Syndrome. Secondary Objectives: To assess: - durability of the antibody response - the SARS-CoV-2-specific T and B cell response - adverse events Exploratory Objectives: To assess: - the association between baseline (immune) parameters and the immune response to SARS-CoV-2 vaccination - the neutralizing capacity of anti-COVID-19 antibodies produced after vaccination - the incidence of SARS-CoV-2 infection and outcome of COVID-19 disease 12 months after SARS-CoV-2 vaccination. - fucosylation of anti-COVID-19 IgG-antibodies in participants with a history of mild or severe SARS-SoV-2 infection CONSORTIUM This study will be performed by a consortium of experts in the field of DS in adults, DS in children, immune responses in DS, COVID vaccine development and the Down Syndrome Society of the Netherlands. STUDY DESIGN We will perform a prospective, observational parallel cohort study. People with DS will be compared to age-matched healthy controls (HC). Two studies will be distinguished: study A (adults, initially) and study P (paediatrics). If adult responses are normal, then it is likely that vaccine responses in children will also be normal. Therefore, a condition to start Study P and the intervention study to administer a 3rd vaccination (2nd booster) is a =20% decrease in levels of antibodies against S following the second vaccination (primary endpoint). STUDY POPULATION We will include adults and children with DS and (HC) from the homes of the people with DS. For pragmatic reasons study A will be started first. Inclusion and exclusion criteria for Study A and Study P are: Inclusion All patients who have opted to receive routine COVID-19 vaccination with age >=17 years (study A) or <=16 years (study P) with DS (DS cohort) or age-matched HC living in the same homes (families or facilities). Exclusion DS cohort: History of severe adverse reaction associated with a vaccine and/or severe allergic reaction; organ transplant recipients, active malignancy or completion of treatment for malignancy in previous 3 months; infection with Human Immunodeficiency Virus (HIV). HC cohort: as in DS cohort plus active care for inherited or acquired immune deficiency, any moderate to severe comorbidity for which regular medical care is needed (p.e. heart disease, COPD, diabetes). Sample size: we will recruit 50 participants with DS and 10 HC per age stratum (18-29; 30-39;40-49;=50 years) for study A. If the conditions to start study P are met, we will recruit 300 children and 100 HC for study P. MEASUREMENTS Venous blood will be drawn before and after routine SARS-CoV-2 vaccination at 4 time points: baseline (t=1, < 2 months prior to first vaccination); t=2: <1 week prior to second vaccination; t=3: 28 days after second vaccination; t=4: 6 months after second vaccination. Peripheral blood mononuclear cells (PBMCs) will be isolated and stored. In serum, we will measure IgG levels against the spike (S) protein of SARS-CoV-2. Antibodies will also be measured at all time points in saliva. General phenotyping of PBMCs will be performed on a relevant subset of =10 participants per age stratum from both groups. We include determination of the concentration of naïve T-cells. Extensive specific (memory) T-cell and B-cell responses to S-peptide pools will be determined using existent assays developed by the National Institute of Health (NIH). MAIN STUDY PARAMETERS/ENDPOINTS The primary endpoint is the serum concentration of SARS-CoV-2-specific antibodies (directed against the spike protein) at t=3 (on day 28 after the second vaccination) as measured by the multiplex immune assay (MIA) developed by the National Institute for Public Health and the Environment (RIVM). Participants will be classified as responders or non-responders. The definition of response will be based on the latest available “correlate of protection” 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 group versus the healthy siblings will be compared. Secondary endpoints include longevity of the immune response at 28 days and 12 months and levels of SARS-CoV-2 specific T and B cell responses. We will relate IgG-glycosylation in previously exposed participants to disease severity in both studies in both cohorts.