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Het combineren van COVID-19 vaccinaties zou

1. vaccinatie campagnes kunnen versnellen

2. de impact van leveringsproblemen kunnen verminderen

3. theoretisch een hogere (meer antilichamen) en een bredere (tegen meer varianten) immuunrespons kunnen uitlokken.


In de SWITCH studie ligt de focus op het toedienen van een tweede coronavaccinatie aan ziekenhuismedewerkers, die eerder eenmalig met Janssen zijn gevaccineerd.



In dit onderzoek wordt gekeken wat het effect van een tweede homologe of heterologe coronavaccinatie is na eenmalig Janssen op zowel de immuunrespons als het optreden van bijwerkingen.



Deelnemers zijn willekeurig ingedeeld in een van de volgende groepen:

1. Geen extra vaccinatie;

2. Een tweede dosis met Janssen;

3. Een tweede dosis met Pfizer;

4. Een tweede dosis met Moderna.


Er wordt bloed op 4 verschillende tijdstippen afgenomen: dag 0 (vóór 2e vaccinatie), dag 28 (primaire eindpunt), na 6 en 12 maanden.

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Eerste resultaten

De eerste resultaten van de SWITCH studie (28 dagen na boost) zijn gepubliceerd in de New England Journal of Medicine op 19 januari 2022. De resultaten laten zien dat verschillende combinaties van booster vaccinaties goed worden verdragen bij gezonde mensen die 1x zijn gevaccineerd met Janssen. Het toedienen van een boostervaccinatie met een mRNA vaccin (Moderna of Pfizer) na een Janssen-vaccinatie laat een hogere response zien in vergelijking met het toedienen van 1 of 2 Janssen-vaccinaties.


Het 6-maanden tijdpunt is 1 maand vervroegd vanwege overheidsmaatregelen. Op dit moment zijn we de 5-maanden data na boost aan het analyseren.

Samenvatting van de aanvraag

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Introduction: The first vaccines against COVID-19 were available in the Netherlands from January 2021. The ability to combine vaccinations could make vac-campaigns more flexible in the future. It could speed up the process and reduce the impact of supply disruptions. It can also elicit a broader immune response (in terms of neutralizing antibodies and T-cell responses). These results support the need to conduct clinical trials in humans to investigate the safety and immunogenicity of heterologous vaccination regimens. Several studies have already been set up to look at the safety and immunogenicity of a heterologous vaccination regimen. These studies are ongoing in the UK and Spain where they are combining Pfizer and AstraZeneca and vice versa (Com-COV & CombiVacS). For these reasons, we decided to focus our study on adeno priming with Janssen, which is not studied in other ongoing studies. As the vaccination rate in The Netherlands is increasing rapidly, we decided to include HCW vaccinated once with Janssen.



Measuring the SARS-CoV-2-specific immune response against SARS-CoV-2 after vaccination with Janssen compared to a homologous vaccination regimen with Janssen /Janssen and the comparison of a homologous vaccination regimen (Janssen/Janssen) with a heterologous vaccination regimen (Janssen/Pfizer + Janssen/Moderna).



A multicentre, randomized, single-blind, controlled study. Only registered, available vaccines will be administered (Pfizer, Moderna and Janssen). At inclusion participants (already vaccinated once with Janssen are randomized to a single dose (i.e no 2nd vaccination), homologous vaccination strategy (two of the same vaccines) or a heterologous vaccination strategy (two different vaccines). Blood will be drawn at 4 timepoints: day 0 (before 2nd vaccination), day 28 (primary endpoint), day 180 (+/-14 days) and day 365 (+/-14 days). The primary outcome parameter is similar to the other studies (humoral response at 28 days after 2nd vaccination). Questionnaires will be used to check for adverse events after each vaccination and to evaluate any breakthrough SARS-CoV-2 infections and outcome despite vaccination.


Main endpoint

The immune response to SARS CoV-2 28 days after the second vaccination is the primary endpoint.



Healthcare Workers (HCW) from 18 to 65 years old vaccinated once with Janssen. Given the speed of the Dutch vaccination campaign, it is not feasible to collect baseline immunological data before first vaccination. For this reason, the baseline in this study is at the day of the booster (second) vaccination. If we cannot recruit enough HCW within the recruiting hospitals, we expand our population to HCW in surrounding peripheral hospitals and primary care (e.g., local pharmacies, dental practices, and physiotherapists).



Since a number of studies are already underway into the use of vaccinations in vulnerable patient groups in the Netherlands and several international heterologous vaccination strategies are studied abroad, it has been decided to use the same study design as much as possible. We looked in particular at VACOPID and VOICE, but also Com-COV and Combivacs.


Burdens / risks associated with participation

In line with current policy, all HCW will be vaccinated at scheduled times, this does not create any additional burden compared to standard care. The burden for participation in the study lies in the fact that blood will be taken at different time points and a number of questionnaires (side effects and exposure to / infection with Sars-CoV-2) must be completed.

If a heterologous vaccination strategy leads to insufficient protection (titer of neutralizing antibodies), this will become apparent within one month after the 2nd vaccination. If this happens, adequate measures will be taken to ensure the safety of hospital staff.


HCW participation

The target group of this study consists of HCW. A sounding board group (SBG) will be formed for more intensive involvement of the target group. This SBG will consist of at least Ellen de Haas as chairman (Member of the Works Council Erasmus MC). In addition, a HCW will be appointed from each participating hospital. If we are forced to shift to primary care community pharmacists will be approached. Every month during the study this SBG will meet with representatives of the researchgroup.


Communication / implementation

Both primary endpoint and long-term data will be published in several high-impact articles in major peer-reviewed medical journals.

For implementation various members of the research group are involved with RIVM/OMT/VWS/Health Council and WHO. Results will be brought in by the active parties involved and put on the agenda in the various forums. In addition, the results will be actively managed and submitted to both the RIVM/OMT/VWS/health council.

Matthew Snape has invited us to join a COVAX meeting, which will facilitate the distribution of our knowledge as well.


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