Evaluating a full or fractional third dose of COVID-19 vaccines in previously vaccinated adults

INTERVENTION: Study participants will be randomly allocated to receive one of the following at visit 1: a fractional dose of Pfizer/Wyeth or AstraZeneca/Fiocruz vaccines, or full dose AstraZeneca/Fiocruz vaccine given at least 4 months (120 days) after two doses of Sinovac/Butantan. Participants, laboratory staff, and clinicians assessing causality will be blinded to the treatment allocation. Randomisation will be performed using a secure internet‐based randomisation system ensuring allocation concealment by a member of the local research team. Participants will be allocated in a 1:1:1 ratio. CONDITION: The administration of fractional dose of Pfizer/Wyeth or AstraZeneca/Fiocruz vaccines for prevention of COVID‐19 when used as an additional dose in adults aged 18 years or older who have received 2 doses of Sinovac/Butantan, at least 4 months (120 days) prior to administration of booster. ; Infections and Infestations PRIMARY OUTCOME: ; 1. Sororesponse is measured using anti‐Spike IgG seroresponse rate (SRR)* in the fractional and full dose arms. *SRR is defined as: 4‐fold rise in GMTs at 28 days post study vaccine from baseline among participants with detectable Ab titers pre‐booster; OR detectable Ab titres at 28 days post study vaccine among participants with no pre‐dose detectable titres.; 2. Safety and reactogenicity are measured using an electronic diary completed by participants in the 7 days following visit 1and up to 28 days if unsolicited adverse events occur. Solicited systemic adverse events include fever, chills, joint pains, muscle pains, fatigue, headache, nausea, and loss of appetite. Occurrence of SAEs and AESIs will be followed throughout the Trial.; SECONDARY OUTCOME: ; 1. Humoral immune response measured using geometric mean titre (GMT) and geometric mean fold rise (GMFR) for binding neutralizing antibody titres at day 0, day 28 and day 182.; 2. Humoral immune response measured using seroresponse rate (SRR) based on neutralising antibody titres at day 0, day 28 and day 182.; 3. Cellular immune responses measured by ELISpot and ICS (Th1/Th2) at day 0, day 28 and day 182.; INCLUSION CRITERIA: 1. Males or females aged 18 years old or above. 2. Participants willing and able to comply with the study procedure. 3. Participants willing and able to provide informed consent prior to screening. 4. Participants who received two Sinovac/Butantan vaccine doses at least 4 months (120 days) prior to enrolment in this study, with a dose interval between each Sinovac/Butantan dose of 14‐28 days (+ 7 days). 5. For females of childbearing potential: willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of screening and vaccination.