Queensland COVID-19 Vaccination (QoVAX) Safety and Efficacy Trial Program: Mixed Dose 1 and 2 Study

The primary outcome measure is serum IgG spike concentration at 4-6 month post vaccine Dose 2, and 4 weeks after the COVID-19 booster dose. The comparison of interest is heterologous compared to homologous vaccine groups. Data will be analysed using a General Linear Model with log-normal distribution to compare (log) fold-increase in serum IgG. Treatment group, vaccine type given at Dose 1 and 2, and age will be used as covariates to adjust for potential confounding given ATAGI has recommended the AZ vaccine for older and Pfizer for younger individuals. Values below the limit of detection (LoD) of the test will be replaced by values equal to the LoD divided by two. No replacement of missing data will be considered for the primary outcome. Univariate analysis will be used to explore the relationships between IgG and host intrinsic and extrinsic factors, pre-existing health conditions, medications and vulnerable groups. Additional exploratory descriptive analysis including IgG to SARS-CoV-2 nucleocapsid, HLA-type, gender, immunocompetence and ethnicity as covariates are planned. Secondary outcomes include for a subset of patients: neutralizing antibody titres, serum and salivary IgA levels, and cell mediated immunity to original vaccine strain. Descriptive comparative analysis between Groups 1 and 2 and other targeted subgroups for the primary outcomes will also be undertaken. Medium-term health analysis of participants will be evaluated by integration of result test results with vaccine notification data to investigate vaccine efficacy outcomes in relation to immune response and data on other health and social determinants.