EU-COVAT-2 BOOSTAVAC

To determine the need for, optimal timing of, and immune response after administering a 4th homologous vaccination dose against SARS-CoV-2 in the general population (18+ years) already vaccinated with the BNT162b2 vaccine.

• To determine the change in cellular immune response measured by a direct from blood qPCR based T-cell activation (dq-TACT) assay at 14 days after 4th dose vaccine in comparison to prior to 4th dose vaccination
• To correlate humoral immune response, cellular immune responses and viral neutralising capacity against wild type SARS-CoV-2
• To determine the durability of humoral and cellular immune responses after 3rd dose of initial vaccination and 4th dose vaccination
• To determine rates of, and maximum disease severity associated with confirmed SARS-CoV-2 infections occurring after enrolment in study participants before and after 4th dose vaccine
• To explore primary and secondary endpoints stratified by incident infection pre-4th dose vaccine or by any modification of vaccine epitope

• Adults aged 18 years or above at baseline
• Be at least 3 and no more than 6 months (+/- 4 weeks) from the date of third dose of BNT162b2 vaccine at the time of consent
• Have received three homologous doses as primary vaccination against SARS-CoV-2 with BNT162b2 vaccine (vaccination status should be documented).
• Written informed consent from the subject has been obtained.

• Unable to provide written, informed consent
• Participation in any other interventional trials
• People who have already received a booster vaccination
• Any significant or uncontrolled disease posing a risk with vaccination as judged by the investigator (including recent, confirmed positive SARS-CoV-2 test within the previous three weeks)
• Any significant medical condition that in the opinion of the investigator would necessitate booster vaccination against SARS-CoV-2 within the trial timelines
• Any kind of dependency on the sponsor or principal investigator or employed by the sponsor or principal investigator
• Where a subject's primary vaccination and third dose vaccination was not with the BNT162b2 mRNA vaccine
• Any contraindication to the vaccines in the trial as per the Summary of Medicinal Product Characteristics, SmPC) or the Investigator’s Brochure, if appropriate. A list of contraindications (including prior anaphylaxis to BNT162b2) are listed in the SmPC
• Use of drugs with significant interaction with the investigational product as per the SmPC
• Subjects who are pregnant and who are planning to become pregnant
• Nursing mothers
• Unwillingness to use highly effective contraceptive methods. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective:

o Oral hormonal contraception Protocol code: UCDCRC/21/10_Version 2.2_17-Jan-2022 22/73 o Dermal hormonal contraception o Vaginal hormonal contraception (NuvaRing®)

o Contraceptive plaster o Long-acting injectable contraceptives

o Implants that release progesterone (Implanon®)

o Tubal ligation (female sterilisation)

o Intrauterine devices that release hormones (hormone spiral)

o Double barrier methods

This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus).

4th dose of BNT162b2 administered at a number of time points from baseline visit:

• Arm 1: control (no booster vaccination)
• Arm 2: booster at month 0
• Arm 3: booster at month 2
• Arm 4: booster at month 4
• Arm 5: booster at month 6

Single dose, intramuscular administration of vaccine.

4th dose of BNT162b2 administered at a number of time points from baseline visit. Following completion of the Screening visit procedures and confirmation of eligibility, sites will access the randomisation tool for assignment of the study arm (control group or vaccination at either month 0, 2, 4 or 6).

All subjects will attend the Baseline visit (month 0) up to 28 days after the screening visit. Eligibility will be reviewed at this visit. 

Subjects randomised to an intervention will receive a single dose of BNT162b2 vaccine at month 0, 2, 4 or 6 after enrolment as per the allocated study arm.

Follow up of subjects included will last for up to 7 months after enrolment.