The goal of this clinical trial is to compare different Coronavirus Disease 2019 (COVID-19) vaccination schedules in healthy adults that have not yet been exposed to SARS-CoV-2, the virus causing COVID-19. The main questions it aims to answer are:

1. Is it possible to adapt COVID-19 vaccination schedules while maintaining an adequate humoral immune response?
2. Is it possible to adapt COVID-19 vaccination schedules while maintaining an acceptable safety profile?

Participants will be vaccinated twice with a COVID-19 vaccine (on day 0, and on day 28 or 84). After each vaccination, they will collect information about adverse events in a diary for 14 days. Information about the occurrence of events such as hospitalizations and infections with SARS-CoV-2 will be collected by the investigator for up to 364 days after the first vaccination. Blood samples will be taken on different timepoints and used to assess immunity against SARS-CoV-2.

Researchers will compare 8 vaccination schedules to see if the immune response and safety profile is similar. Each participant will receive 1 of the following 8 vaccine schedules:

• BNT162b2 (30µg) on day 0, followed by BNT162b2 (30µg) on day 28
• BNT162b2 (20µg) on day 0, followed by BNT162b2 (20µg) on day 28
• BNT162b2 (30µg) on day 0, followed by BNT162b2 (30µg) on day 84
• BNT162b2 (30µg) on day 0, followed by mRNA-1273 (100µg) on day 28
• BNT162b2 (30µg) on day 0, followed by ChAdOx1-S [recombinant] on day 28
• BNT162b2 (6µg, intradermal administration) on day 0, followed by BNT162b2 (6µg, intradermal administration) on day 28
• mRNA-1273 (100µg) on day 0, followed by mRNA-1273 (100µg) on day 28
• mRNA-1273 (50µg) on day 0, followed by mRNA-1273 (50µg) on day 28

Inclusion Criteria:

1. Male, female, or X (non-binary gender) subjects, 18-55y inclusive on the day of signing of the ICF

2. Provision of signed and dated informed consent form

3. Available at all provided timepoints of the study and is not planning to move abroad for the whole duration of the study

4. In good general health as evidenced by medical history and/or physical examination or adults with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment.

5. Willing and able to comply with all study procedures

6. Participants born female must be either:

   • of childbearing potential and using effective contraception for at least 1 month prior to screening and agree to use such a method during study participation until 1 months following the last study dose administration.
   • of non-childbearing potential.

Exclusion Criteria:

1. Previous clinical or microbiological confirmed diagnosis of COVID-19.
2. Febrile illness within 72hours before first vaccination (this is a temporary exclusion criterion).
3. Unstable, severe, progressive disease in the past 3 months.
4. History of malignancy during the past 5 years.
5. History of severe adverse reaction associated and/or anaphylaxis with a vaccine.
6. Known allergic reactions of any severity to polyethylene glycol [PEG] or to polysorbate (due to potential cross-reactive hypersensitivity with the vaccine ingredient PEG).
7. Primary or secondary immunodeficiency disorders (e.g. immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection…).
8. Chronic administration (defined as more than 14 days in total) of immunosuppressant or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone 20 mg/day, or equivalent. Inhaled, nasal, opthalmic and topical steroids are allowed.
9. Pregnancy or lactation.
10. History of drug or alcohol abuse.
11. Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk, including relevant psychiatric diagnosis.
12. Previous vaccination or planned to accept other vaccination during this study with any coronavirus vaccine outside this study.
13. Previous vaccination or planned to accept other vaccination during this study with any coronavirus vaccine outside this study, with the exception of a third COVID-19 vaccine during fall/winter '21-'22.
14. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
15. Participation in another clinical trial with an IMP or a new medical device within 28 days prior to study entry and/or during study participation.
16. Participant is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as first degree family members and household members of the employees or the investigator, or an employee of the sponsor.

The datasets used and analyzed during the current study are available from the central contact person on reasonable request, following material transfer agreements.

Datasets will become available - upon request - after publication of the main results in a peer-reviewed scientific journal.

The datasets used and analyzed during the current study are available from the central contact person on reasonable request, following material transfer agreements.

Participants were blinded up to the venous blood draw used to assess the primary endpoint (day 112 for the long-interval treatment arm, day 56 for all other treatment arms). Afterwards, participants were unblinded because the registration of all administered COVID-19 vaccines was required by the Belgian government.