Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity

For dose 1 and 2, the currently available mRNA vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) are two dose vaccines which were studied in schedules of either 0 and 21 days or 0 and 28 days, respectively. The ChAdOx1 nCOV-19 (Astra-Zeneca) adenovirus-vectored vaccine is authorized to be given in two doses one month to 12 weeks apart. We will compare the interval 0, 28 days to a 0, 112 days (16 weeks) schedule, and assess the immunogenicity of both heterogeneous and heterologous second doses using the Canadian schedule.

For dose 3, the currently available mRNA vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and plant-based virus-like particle (Medicago Covifenz) are anticipated to be administered 6 months apart. We will assess the immunogenicity of both heterogeneous and heterologous third doses using the Canadian schedule.

For dose 4, the currently available mRNA vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and plant-based virus-like particle (Medicago Covifenz) are anticipated to be administered 3 months apart. We will assess the immunogenicity of both heterogeneous and heterologous third doses using the Canadian schedule.

Inclusion criteria

• Participant is willing and able to give written informed consent to participate in the study
• Age 18 years of age or older in good health or with mild or moderate stable co-morbidities at the time of enrolment
• Able and willing to complete all the scheduled study procedures during the whole study follow-up period
• If female of child-bearing potential and heterosexually active, has practiced adequate contraception for 30 days prior to injection, has a negative pregnancy test on the day of injection, and has agreed to continue adequate contraception until 3 months after the final dose of study vaccine (Please refer to the definition section for a description of child-bearing potential and adequate contraception)
• MOSAIC-1 Vaccine-exposed subgroups: have received or are booked to receive the first dose of an authorized COVID-19 vaccine in the 55 days prior to Visit 1 (documentation of receipt required)
• MOSAIC -1 Vaccine naïve subgroups: have not received an authorized COVID-19 vaccine at any time
• MOSAIC-2 participants have received two doses of COVID-19 vaccines authorized in Canada ≥6 months prior to study vaccine administration (documentation of receipt required)
• MOSAIC-3 participants have received three doses of COVID-19 vaccines authorized in Canada ≥3 months prior to study vaccine administration (documentation of receipt required)

Exclusion criteria

• Inability or unwillingness of participant or legally acceptable representative to give written informed consent
• Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia, or immunosuppressant medication within the past 6 months except short term oral steroids (≤14 days duration) or topical steroids
• Current diagnosis or treatment for cancer (except basal cell carcinoma of the skin)
• Administration of immunoglobulins and/or any blood products within 3 months preceding the first dose of study vaccine and for one month after the last dose of study vaccine
• Allergy to any study vaccine or any active substance in a study vaccine
• Bleeding disorder or history of significant bleeding following IM injections or venipuncture
• Continuous use of anticoagulants
• A history of anaphylaxis to a previous vaccine
• Pregnancy or intent to become pregnant during the study or within 3 months of the last dose of study vaccine
• MOSAIC-1: History of laboratory-confirmed COVID-19 disease prior to enrolment by participant report
• Administration of a live virus vaccine within 4 weeks prior to study vaccine receipt.