A Multicenter, Randomised, Single-blind, Controlled Trial Among HealthCare Workers (HCW) Vaccinated With Janssen Vaccine: the SWITCH Trial

Rationale: A novel coronavirus (SARS CoV-2) was first detected in Wuhan, China in December 2019 (1). In January 2021 the first vaccines protecting against this virus are available in the Netherlands. Most current available vaccines in the Netherlands (e.g., AstraZeneca vaccine (2), Moderna vaccine (3), and Pfizer vaccine (4) require a second boost (2nd vaccination) after the prime (1st vaccination), to obtain an optimal immune response. The booster (2nd vaccination) has up to present always been given with the same vaccine as the primary vaccine. Unfortunately, the availability of the vaccines is limited and a speedy vaccination is also hampered by logistic reasons. The ability to combine different vaccines could make vaccination programs in the future more flexible. It would facilitate a fast-track process and reduce the impact of any supply-chain disruptions (5). In addition, several studies in mice have already shown that combining different vaccines (two-dose heterologous vaccination regimen) can elicit a broader immune response (in field of neutralizing antibodies and T-cell responses)(6, 7). These results endorse the need for clinical trials to investigate the immunogenicity of heterologous regimens. Trails to combine different vaccines have meanwhile been set up in Great Britain and Spain where they combine Pfizer vaccine and AstraZeneca vaccine (Com-COV 1(8) and CombiVacS(9)). Recently, it became known that the CoM-COV1 was expanded with Moderna vaccine and Novavax vaccine (CoM-COV2(10)). Therefore this protocol has a focus to adeno priming with Janssen vaccine, which is not studied in the other ongoing studies. As the vaccination rate in The Netherlands is increasing rapidly, it was decided to include Healthcare Workers (HCW) vaccinated once with Janssen vaccine. Objective: The key objective of the study is to measure the immune response against SARS-CoV-2 after different vaccinations in Health Care Workers (HCW) from 18 to 65 years old.

Determination of antibodies by a quantitative IgG assay (LIAISON SARS-CoV-2 TrimericS IgG essay) 28 days after second vaccination (booster) comparing, per protocol, the following three groups:

1. Janssen vaccine/- vs. Janssen vaccine/Janssen vaccine
2. Janssen vaccine/Janssen vaccine vs. Janssen vaccine/Pfizer vaccine
3. Janssen vaccine/Janssen vaccine vs. Janssen vaccine/Moderna vaccine Study design: A multicenter, randomised, single-blind, controlled trial to determine reactogenicity and immunogenicity of different prime-boost COVID-19 vaccine schedules.

Setting: multicenter study conducted at 4 academic University Medical Centers (UMC) hospitals (Amsterdam UMC, Erasmus UMC, Leiden UMC, and UMC Groningen).

Hypothesis: Immunogenicity in participants who have already received one dose of Janssen vaccine will be higher when it is followed by a heterologous booster containing Pfizer vaccine or Moderna vaccine as opposed to a homologous booster containing Janssen vaccine.