Anti-viral action against type 1 diabetes autoimmunity: The GPPAD-AVAnT1A study protocol.

Viral infections in the first year of life are associated with islet autoimmunity and type 1 diabetes risk. The Anti-Viral Action against Type 1 Diabetes Autoimmunity (AVAnT1A)- study is a clinical phase IV investigator initiated, randomised, controlled, multicentre, primary prevention trial conducted to determine whether vaccination against COVID-19 from 6 months of age reduces the cumulative incidence of islet autoantibodies or type 1 diabetes in children with elevated genetic risk. Additionally, it investigates the role of viral infections in the etiology of islet autoimmunity by intense surveillance within the first two years of life. Infants aged 3.00-4.00 months from Germany, Belgium, UK and Sweden are eligible if they have a >10 % expected risk to develop islet autoantibodies by age 6 years as determined by HLA DR/DQ genotype, polygenic risk score and family history of type 1 diabetes. A total of 2252 eligible children are randomized 1:1 to COVID-19 vaccine (Comirnaty® 3 μg Omicron XBB.1.5 or future new variants) or placebo (0.9 % Sodium Chloride) administered three times. Children are followed until the minimum age of 2.5 years and maximum age of 6 years. The intervention is accompanied by analyses of immune and metabolic parameters to determine changes induced by viral infections and to investigate mechanisms by which viral infection may lead to islet autoimmunity. The Sponsor is the Klinikum rechts der Isar, Technical University Munich. The study was approved by Clinical Trials Information System (CTIS, EU Trial number: 2023-507348-35-00) and by Integrated Research Application System (IRAS, IRAS-ID: 1009668).