IMCOVAS: Assessment of the immunogenicity and safety of

Summary (French or Dutch)

Currently, 4 Covid-19 vaccines are approved in the European Union but the supply of vaccines depends on many factors. If due to unforeseen circumstances a particular brand of Covid-19 vaccine is not sufficiently supplied, this could mean a significant delay in the national vaccination campaign. Therefore, this study will investigate the effect on the immune response if the interval between 2 vaccine doses is extended, if another brand of COVID-19 vaccine is used for the 2nd dose (booster) or if half the recommended dose is used. In addition, this study will also investigate whether an injection into the skin (intradermal) with a lower dose can produce a similar immune response as an injection into the muscle of the upper arm (intramuscular) with a normal dose.
For this study, 3 Covid-19 vaccines currently on the market will be used, no placebo will be administered.These vaccines are:
-   BNT162b2 (Comirnaty®; Pfizer-BioNTech)
-   mRNA-1273 Vaccine (COVID-19 Vaccine Moderna®; Moderna)
-   COVID-19 Vaccine (ChAdOx1-S [recombinant]) (Vaxzevria®; AstraZeneca)

There are 3 blocks in this study, each containing multiple study groups. In total, there are 12 study groups. In each block, one group will receive the recommended administration schedule of a particular Covid-19 vaccine. The other groups will receive a different administration schedule: lower dose, different booster vaccine, longer interval between doses or intradermal injection.

Summary of results
At the start of the COVID-19 vaccination campaign, there was still much uncertainty about the available vaccination schedules or potential combinations. Flexibility by combining different brands of vaccines, by adjusting the time between 2 vaccinations or even by lowering the dose of a vaccine may be important when insufficient COVID-19 vaccines can be produced or supplied. The IMCOVAS study evaluated several adapted vaccine schedules between May 2021 and July 2022 to determine whether these could induce the same quantity and quality of antibodies against COVID-19. For this purpose, 566 healthy adults who had not previously experienced COVID-19 were vaccinated according to 1 of the 8 vaccination schedules studied. Study participants were administered 2 COVID-19 vaccines during the study and were followed up to 1 year after the first vaccination to study antibody production, occurrence of adverse events and the occurrence of COVID-19 infections after vaccination. The vaccine schedules used consisted of combinations of Pfizer (BNT162b2), Moderna (mRNA-1273) and AstraZeneca (ChAdOx1-S) COVID-19 vaccines administered at different doses, intervals and via different routes of administration. The schedule assigned to a study participant was determined by chance. Prolonging the interval between 2 Pfizer vaccinations from 28 to 84 days, the use of a Moderna vaccine after an initial vaccination with Pfizer, and a vaccine schedule with a lower dose of the Moderna vaccine were found to induce as many antibodies as the standard proposed schedules. In contrast, slightly fewer antibodies were produced after administration of the vaccine in the skin than after administration in the muscle of the upper arm. For all vaccine schedules, a clear production of additional antibodies was seen after a first booster vaccination, and a similar rate of COVID-19.

Summary of results

At the start of the COVID-19 vaccination campaign, there was still much uncertainty about the available vaccination schedules or potential combinations. Flexibility by combining different brands of vaccines, by adjusting the time between 2 vaccinations or even by lowering the dose of a vaccine may be important when insufficient COVID-19 vaccines can be produced or supplied. The IMCOVAS study evaluated several adapted vaccine schedules between May 2021 and July 2022 to determine whether these could induce the same quantity and quality of antibodies against COVID-19. For this purpose, 566 healthy adults who had not previously experienced COVID-19 were vaccinated according to 1 of the 8 vaccination schedules studied. Study participants were administered 2 COVID-19 vaccines during the study and were followed up to 1 year after the first vaccination to study antibody production, occurrence of adverse events and the occurrence of COVID-19 infections after vaccination. The vaccine schedules used consisted of combinations of Pfizer (BNT162b2), Moderna (mRNA-1273) and AstraZeneca (ChAdOx1-S) COVID-19 vaccines administered at different doses, intervals and via different routes of administration. The schedule assigned to a study participant was determined by chance. Prolonging the interval between 2 Pfizer vaccinations from 28 to 84 days, the use of a Moderna vaccine after an initial vaccination with Pfizer, and a vaccine schedule with a lower dose of the Moderna vaccine were found to induce as many antibodies as the standard proposed schedules. In contrast, slightly fewer antibodies were produced after administration of the vaccine in the skin than after administration in the muscle of the upper arm. For all vaccine schedules, a clear production of additional antibodies was seen after a first booster vaccination, and a similar rate of COVID-19.

TRIAL DESCRIPTION

Title	Assessment of the immunogenicity and safety of marketed vaccines for COVID-19 after regular schedule and adapted vaccine schedules and routes: Comirnaty® (Pfizer), Covid-19 vaccine Moderna® (Moderna) and Vaxzevria® (AstraZeneca) - IMCOVAS
Participants (P)	healthy adults 18-55y
Intervention (I)	12 arms in total: BNT162b2 (Comirnaty®;Pfizer-BioNTech): 30 mcg (IM), 20 mcg (IM) and 6mcg (ID) mRNA-1273 Vaccine (COVID-19 Vaccine Moderna®; Moderna): 50mc (IM) COVID-19 Vaccine (ChAdOx1-S [recombinant]) (Vaxzevria®, AstraZeneca): 0.5mL (IM), 0.25mL (IM) and 0.1mL (ID) – only for 41-55 years old 1 prime dose and 1 boost dose. In case of a standard dose, boost dose can be of a different brand than prime dose or longer schedule between two doses . Route: IM or ID
Control (C)	Reference schedule of the 3 marketed vaccines BNT162b2 (Comirnaty®;Pfizer-BioNTech): 30 mcg (IM) mRNA-1273 Vaccine (COVID-19 Vaccine Moderna®; Moderna): 100mcg (IM) COVID-19 Vaccine (ChAdOx1-S [recombinant]) (Vaxzevria®, AstraZeneca): 0.5mL (IM)
Outcome (O)	Geometric Mean Titre of antibodies binding to the Receptor Binding Domain of SARS-CoV-2 S protein 28 days post last vaccine dose
Trial Design	A prospective, post marketing, randomized multicentre interventional study
Sample Size	840 healthy volunteers
Trial duration	19 months
Budget	€2.9 MIO

TRIAL TEAM

Sponsor	University of Antwerpen
Chief Investigator	Dr Katie Steenackers
External partners	Institute of Tropical Medecine
Number of participating sites	4
Participating investigators	Dr Katie Steenackers (CEV – UA) Prof. Dr. Isabel Leroux-Roels (CEVAC – UZ Gent) Dr. Patrick Soentjens (ITM) Prof. Dr. Maya Hites (Erasme)