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.

本研究的主要结局指标为第2剂疫苗接种后4~6个月，以及新冠疫苗加强针接种后4周时的血清刺突蛋白（spike protein）IgG（免疫球蛋白G）浓度。本研究关注的组间比较为异源疫苗接种方案与同源疫苗接种方案组之间的对比。数据将采用服从对数正态分布的广义线性模型（General Linear Model）进行分析，以对比血清IgG的（对数）倍数变化。考虑到澳大利亚免疫技术咨询小组（Australian Technical Advisory Group on Immunisation, ATAGI）建议老年人接种阿斯利康（AstraZeneca, AZ）疫苗、年轻人接种辉瑞（Pfizer）疫苗，本研究将以治疗组、第1、2剂接种的疫苗类型以及年龄作为协变量，校正潜在的混杂因素。检测结果低于检测限（Limit of Detection, LoD）的样本，将以LoD的一半数值进行替换。针对主要结局指标，不考虑对缺失数据进行补全。将采用单变量分析，探究IgG水平与宿主内外源性因素、基础健康状况、用药情况以及脆弱人群特征之间的关联。计划开展额外的探索性描述性分析，纳入分析的协变量包括新冠病毒核衣壳蛋白IgG、人类白细胞抗原（Human Leukocyte Antigen, HLA）分型、性别、免疫功能状态以及种族。次要结局指标针对部分受试者，涵盖中和抗体滴度、血清与唾液IgA水平，以及针对原始疫苗株的细胞介导免疫反应。同时还将针对第1、2组及其他预设亚组的主要结局指标开展描述性对比分析。将通过整合受试者的检测结果与疫苗接种报备数据，开展受试者的中期健康分析，以探究与免疫反应相关的疫苗效力结局，以及其他健康与社会决定因素相关的数据。