SWITCH ON: Analysing the Immunogenicity of Additional Booster Vaccinations in HCW

Study Overview
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Brief Summary
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Eighty percent of the Dutch population has completed a primary COVID-19 vaccination regimen, and 60% of the population received a booster vaccination. Waning immunity, combined with the emergence of antigenically distinct SARS-CoV-2 variants, has led to the consideration of additional booster vaccinations in the Dutch population by autumn 2022. However, despite efforts of the Dutch policymakers, the public's willingness to repeatedly receive COVID-19 booster vaccinations is declining. This is mainly due to a reduced burden of disease by COVID-19, fewer hospitalizations, and fewer deaths. However, population immunity might be one of the major factors responsible for this reduced burden of disease, possibly emphasizing the need for booster vaccinations. In this proposal we will address an important question asked by policymakers: Are booster vaccinations in autumn recommended for the healthy population?

Official Title
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SWITCH ON: Analysing the Immunogenicity of Additional Booster Vaccinations in Healthcare Workers. A Multicenter, Randomised, Controlled Trial

Conditions
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Covid-19 Vaccination

Intervention / Treatment
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* Drug: Direct boost mRNA
* Drug: Direct boost adeno
* Drug: Post-poned boost mRNA
* Drug: Post-poned boost adeno


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to give written informed consent for participation in the trial. Adult (male/female) between 18 and 65 years old Sufficient level of the Dutch language to undertake all study requirements Exclusion Criteria: Adults younger than 18 or older than 65 years. Adults primed with another vaccine than Janssen, Moderna or Pfizer. History of allergic reactions likely to be exacerbated by any component of study vaccines (e.g. hypersensitivity to the active substance or any of the SmPC-listed ingredients of the Janssen/Pfizer/Moderna vaccine). Adults that are pregnant. Currently being treated for cancer. Severe kidney failure or dialyses dependent. Status after organ-, stem cell- or bone marrow transplantation. Use of immunosuppressant's. Epilepsy. HIV. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding of bruising following IM injections of vene puncture. Continuous use of anticoagulants, such as coumarins (e.g. acenocoumarol) or novel oral anticoagulants (i.e. apixaban, dabigatran etc). Participants who are currently participating in another research trial. All regular contra-indications of the vaccines will be applied.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 67 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multicenter, randomized, controlled trial comparing immune responses 7 and 28 days after an additional COVID-19 booster vaccination between Janssen and mRNA primed HCWs to describe the immune response in a cohort representative of the Dutch population, in order to eventually provide data for Dutch policy makers
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Direct boost mRNA<br>Participants will be randomised into a direct boost group (DB; i.e end of August) or a post-poned boost group (PPB; i.e 3-4 months later) group after stratification for priming (mRNA versus Janssen). The immune response will be measured at start of the study (visit 1, all participants) and 0, 7, 28 and 84 days after boost. | Drug: Direct boost mRNA<br>* Participants will be boosted with a covid-19 vaccin after priming with mRNA<br>|
| Active Comparator: Direct boost adeno<br>Participants will be randomised into a direct boost group (DB; i.e end of August) or a post-poned boost group (PPB; i.e 3-4 months later) group after stratification for priming (mRNA versus Janssen). The immune response will be measured at start of the study (visit 1, all participants) and 0, 7, 28 and 84 days after boost. | Drug: Direct boost adeno<br>* Participants will be boosted with a covid-19 vaccin after priming with adeno<br>|
| Active Comparator: Post-poned boost mRNA<br>Participants will be randomised into a direct boost group (DB; i.e end of August) or a post-poned boost group (PPB; i.e 3-4 months later) group after stratification for priming (mRNA versus Janssen). The immune response will be measured at start of the study (visit 1, all participants) and 0, 7, 28 and 84 days after boost. | Drug: Post-poned boost mRNA<br>* Participants will be boosted with a covid-19 vaccin after priming with mRNA<br>|
| Active Comparator: Post-poned boost adeno<br>Participants will be randomised into a direct boost group (DB; i.e end of August) or a post-poned boost group (PPB; i.e 3-4 months later) group after stratification for priming (mRNA versus Janssen). The immune response will be measured at start of the study (visit 1, all participants) and 0, 7, 28 and 84 days after boost. | Drug: Post-poned boost adeno<br>* Participants will be boosted with a covid-19 vaccin after priming with adeno<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Is there an increase in antibody levels between day of boost and 28 days after boosting HCW that were initially primed with either the Janssen or an mRNA-based vaccine? | Outcome: Level and fold change of antibodies determined by a quantitative IgG assay comparing the Janssen primed and mRNA-based primed HCW. | 28 days | 
| Does booster vaccination lead to a rapid secondary recall response, indicative of immunological memory? | Outcome: Level and fold change of antibodies and T-cell responses determined by a quantitative IgG assay and whole blood IFNγ release assay, respectively, comparing day 7 and 28 post-boost. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| What is the difference in booster immunogenicity comparing a direct boost with a postponed boost? | Outcome: Level of antibodies and T-cell responses 7 and 28 days post boost in DB versus PPB group. | 28 days | 
| What is the breadth of the immune responses after booster vaccination? | Outcome: PRNT against relevant variants in a random selection of study participants. | 28 days | 
| What is the predictive value of immune responses on day 7 post boost? | Outcome: Correlation between antibodies and T-cell responses on day 7 and 28 post boost in % of the 28 day response for both level of antibodies and T-cell responses | 28 days | 
| What is the difference in reactogenicity 7 days after boost comparing the Janssen and mRNA primed HCW? | Outcome: Adverse events (AE) first 7 days after an additional boost between Janssen and mRNA primed HCW. | 7 days | 
| Initial examination of breakthrough infections before and during study period | Outcome: Database of breakthrough infections in included participants based on positive PCR, self-reported positive lateral flow test, or detection of N-specific antibodies. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid-19, Boost