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

Not Applicable

Active, not recruiting

• Conditions: Covid-19 Vaccination
• Interventions: Drug: Post-poned boost adeno; Drug: Direct boost adeno; Drug: Direct boost mRNA; Drug: Post-poned boost mRNA

• Registration Number: NCT05471440
• Lead Sponsor: Erasmus Medical Center

Brief Summary

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?"

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-17
• Study First Submitted QC: 2022-07-21
• Study First Posted: 2022-07-22
• Study Start: 2022-08-20
• Primary Completion: 2022-09-15
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-13
• Last Update Posted: 2023-02-15
• Study Completion: 2023-08-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 431

Inclusion Criteria

1. Participant is willing and able to give written informed consent for participation in the trial.
2. Adult (male/female) between 18 and 65 years old
3. Sufficient level of the Dutch language to undertake all study requirements

Exclusion Criteria

1. Adults younger than 18 or older than 65 years.
2. Adults primed with another vaccine than Janssen, Moderna or Pfizer.
3. 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).
4. Adults that are pregnant.
5. Currently being treated for cancer.
6. Severe kidney failure or dialyses dependent.
7. Status after organ-, stem cell- or bone marrow transplantation.
8. Use of immunosuppressant's.
9. Epilepsy.
10. HIV.
11. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding of bruising following IM injections of vene puncture.
12. Continuous use of anticoagulants, such as coumarins (e.g. acenocoumarol) or novel oral anticoagulants (i.e. apixaban, dabigatran etc).
13. Participants who are currently participating in another research trial.
14. All regular contra-indications of the vaccines will be applied.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Post-poned boost adeno	Post-poned boost adeno	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.
Direct boost adeno	Direct boost adeno	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.
Direct boost mRNA	Direct boost mRNA	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.
Post-poned boost mRNA	Post-poned boost mRNA	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.

Primary Outcome Measures

Name	Time	Method
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?	28 days	Outcome: Level and fold change of antibodies determined by a quantitative IgG assay comparing the Janssen primed and mRNA-based primed HCW.
Does booster vaccination lead to a rapid secondary recall response, indicative of immunological memory?	28 days	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.

Secondary Outcome Measures

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

Trial Locations

Locations (4)

UMCG; 🇳🇱 Groningen, Netherlands

LUMC; 🇳🇱 Leiden, Netherlands

AmsterdamUMC; 🇳🇱 Amsterdam, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Netherlands