An Observer-blind, Cohort Randomized, Exploratory Phase 3 Study to Evaluate the Safety and Immunogenicity of Recombinant Covid-19 Vaccine, mRNA Covid-19 Vaccine and Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine as 4th Dose in Individuals Primed/ Boosted With Various Regimens

1. Individuals with fever \>37.5°C (axillary), or any acute illness at baseline (Day 0) or within 3 days prior to randomization. Participants meeting this criterion may be rescheduled within the relevant window. Febrile participants with minor illnesses can be enrolled at the discretion of the investigator.

2. Individuals who have received more than 3 combined doses of any licensed or experimental COVID vaccine prior to Day 0 or plan to receive COVID-19 vaccine during the study period, a drug for COVID-19 prevention or treatment (e.g., drugs, monoclonal antibodies, such as Rituximab or any other anti-CD20 monoclonal antibodies during the study period.).

3. Receipt of any authorized or investigational COVID-19 vaccine prior to Day 0 except for the 03 doses of Pfizer/ Wyeth; 03 doses of AstraZeneca/Fiocruz; or two doses of Sinovac/Butantan and 01 dose of Pfizer/Wyeth, or eventually 03 doses of Sinovac/Butantan; or two doses of AstraZeneca and one dose of Clover SCB-2019 ≥ 4 months before enrollment in this study.

4. Individuals who have a history of severe adverse reaction associated with a vaccine or severe allergic reaction (e.g., anaphylaxis) to any component of the study vaccines (Pfizer/Wyeth, AstraZeneca/Fiocruz, CpG 1018, aluminum, or SCB-2019 components as outlined in the latest summary of product characteristics for Pfizer/Wyeth, AstraZeneca/Fiocruz and the IB for SCB-2019.

5. Individuals with known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular injection.

6. Individuals who have a history of malignancy within 1 year before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix which have been cured, or other malignancies with minimal risk of recurrence).

7. Individuals with any progressive or severe neurologic disorder, seizure disorder, or history of Guillain-Barré syndrome.

8. Individuals who received treatment with immunosuppressive therapy in the last 90 days, including cytotoxic agents or systemic corticosteroids, or planned receipt during the study period. If a short-term course of systemic corticosteroid immunosuppressive dose has been used for the treatment of acute illness, the participant should not be included in the study until corticosteroid therapy has been discontinued for at least 15 days prior to first study vaccination. If the participant has used an immunosuppressive dose of a depot corticosteroid, intra-muscular or intra-articular, they must wait 60 days for inclusion in the study. Inhaled or nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

9. Individuals with autoimmune diseases, except: Hashimoto's thyroiditis, vitiligo, psoriasis, lupus discord and alike; HIV-positive individuals and/or on HIV treatment.

10. Individuals who have received any other investigational product within 30 days prior to Day 0 or intend to participate in another clinical study at any time during the conduct of this study.

11. Individuals who have received any other licensed vaccines within 14 days prior to enrollment in this study or who are planning to receive any vaccine up to 28 days after the last vaccination.

12. Individuals who have received treatment with Rituximab or any other anti-CD20 monoclonal antibodies within 9 months prior to Day 0 or planned during the study period.

13. Administration of intravenous immunoglobulins and/or any blood products within 3 months prior to enrollment or planned administration during the study period.

14. Individuals with any condition that, in the opinion of the investigator, would interfere with the primary study objectives or pose additional risk to the participant.

15. Pregnancy.

What this study is about