A clinical protocol for a German birth cohort study of the Maturation of Immunity Against respiratory viral Infections (MIAI)

Front Immunol. 2024 Sep 17:15:1443665. doi: 10.3389/fimmu.2024.1443665. eCollection 2024.

Abstract

Introduction: 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 inter-population 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.

Methods: 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.

Discussion: 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.

Clinical trial registration: https://drks.de/search/de/trial/, identifier DRKS00034278.

Keywords: IAV; RSV; SARS-CoV-2; anti-viral immunity; birth cohort; microbiota; multi-omics data; respiratory viral infection.

MeSH terms

  • Birth Cohort
  • COVID-19* / immunology
  • Female
  • Germany / epidemiology
  • Humans
  • Infant
  • Infant, Newborn
  • Influenza, Human* / immunology
  • Male
  • Prospective Studies
  • Research Design
  • Respiratory Syncytial Virus Infections* / immunology
  • Respiratory Tract Infections* / immunology
  • Respiratory Tract Infections* / virology

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work is supported by grants from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) to DV (VI 538-9-1), CH (HA-6409-5-1) and TU (UL 521/1-1). The following other funding sources support the project: the Federal Ministry of Education and Research (BMBF) to SP, CH, and DV (PROSPER; 01EK2103B and 01EK2103A, respectively); the DFG to SP (PI 1512/1-3) and DV (VI 538/6-3); the DFG SFB 1583/1 (“DECIDE”) project number 492620490 to DV and SB; the DFG TRR 359 (“PILOT”) project number 491676693 to DV; the DFG Germany`s Excellence Strategy – EXC 2155 ‘RESIST’ – Project ID 390874280 to DV and TP; the BMBF Advanced Clinician Scientist Program (“INTERACT”, project number 01EO2108) to HM. We acknowledge the financial support of SKFS and UL from the German Research Foundation (DFG) under grants FO 1279/7-1 (Fetale Programmierung der Entwicklung des Mikrobioms und Konsequenzen für die Gehirnentwicklung), FO 1279/2-2, and FO 1279/1-2 as part of the Clinical Research Group “Nahrungsmittelallergie und Toleranz (Food@)” for subproject TP 09 - C2 “Data Analysis, Data Integration, and Rule-Based Modeling of Food Allergies.” Further support was provided by the European Union under the Horizon 2020 Research and Innovation Action (RIA) 101095540 IMMEDIATE for the project “Imminent Disease Prediction and Prevention at the Environment Host Interface,” and by the German Federal Ministry of Education and Research (BMBF) under grant 01EK2103C PROSPER for the project “Prevention of Sepsis through Personalized Nutritional Supplementation of S100A8/A9 in Vulnerable Neonates.