Carina Hartmann ¹ Robin Khan ¹ Jennifer Schöning ¹ Maximilian Richter ¹ Maike Willers ² Sabine Pirr ² Julia Heckmann ¹ Johannes Dirks ¹ Henner Morbach ¹ Monika Konrad ¹ Elena Fries ¹ Magdalene Winkler ¹ Johanna Büchel ¹ Silvia Seidenspinner ¹ Jonas Fischer ¹ Claudia Vollmuth ¹ Martin Meinhardt ¹ Janina Marissen ¹ Mirco Schmolke ³ Sibylle Haid ⁴ Thomas Pietschmann ⁴ Simone Backes ⁵ Lars Dölken ² Ulrike Löber ⁶ Thomas Keil ⁵ Peter U. Heuschmann ⁵ Achim Wöckel ¹ Dr. Sagar ⁷ Thomas Ulas ⁸ Sofia Forslund ⁶ Christoph Härtel ¹ Dorothee Viemann ^1*

• ¹ University Hospital Würzburg, Würzburg, Bavaria, Germany
• ² Hannover Medical School, Hanover, Lower Saxony, Germany
• ³ University of Geneva, Geneva, Geneva, Switzerland
• ⁴ Institute of Experimental Virology, Twincore Center for Experimental and Clinical Infection Research GmbH, Hannover, Germany
• ⁵ Julius Maximilian University of Würzburg, Würzburg, Bavaria, Germany
• ⁶ Max Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers (HZ), Berlin, Baden-Wurttemberg, Germany
• ⁷ University of Freiburg, Freiburg, Baden-Wurttemberg, Germany
• ⁸ University of Bonn, Bonn, North Rhine-Westphalia, Germany

Respiratory viral infections (RVIs) are a major global contributor to morbidity and mortality. The susceptibility and outcome of RVIs are strongly age-dependent and show considerable interpopulation differences, pointing to genetically and/or environmentally driven developmental variability. The factors determining the age-dependency and shaping the age-related changes of human anti-RVI immunity after birth are still elusive. We are conducting a prospective birth cohort study aiming at identifying endogenous and environmental factors associated with the susceptibility to RVIs and their impact on cellular and humoral immune responses against the influenza A virus (IAV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MIAI birth cohort enrolls healthy, full-term neonates born at the University Hospital Würzburg, Germany, with follow-up at four defined time-points during the first year of life. At each study visit, clinical metadata including diet, lifestyle, sociodemographic information, and physical examinations, are collected along with extensive biomaterial sampling. Biomaterials are used to generate comprehensive, integrated multi-omics datasets including transcriptomic, epigenomic, proteomic, metabolomic and microbiomic methods. The results are expected to capture a holistic picture of the variability of immune trajectories with a focus on cellular and humoral key players involved in the defense of RVIs and the impact of host and environmental factors thereon. Thereby, MIAI aims at providing insights that allow unraveling molecular mechanisms that can be targeted to promote the development of competent anti-RVI immunity in early life and prevent severe RVIs.