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

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.

Figure 1

Hypothesis of the MIAI study. The hypothesis of the MIAI study is that the maturation of anti-viral immunity toward RVIs in early life underlies a large developmental variability, which is imprinted by clinical and environmental factors such as dietary habits, lifestyle, and particularly the composition and function of the co-evolving respiratory and gut microbiota.

Figure 2

Design MIAI study. The MIAI study encompasses four phases starting with recruitment of term healthy infants and follow-up visits at defined timepoints. At each appointment, clinical data and biomaterials are collected for storage and/or usage in ex vivo respiratory viral infection models. Multi-omics datasets will be generated including immune profiles, transcriptomics, epigenomics, proteomics, metabolomics and microbiomics. To gain clinical and scientific knowledge, overall integration of mixed omics data shall enable participant stratification based on marker patterns linking to RVI susceptibility and reveal host and environmental factors imprinting anti-RVI immunity in the first year of life.

Figure 3

Collection of biomaterials in MIAI. Biomaterials collected in the MIAI cohort include breast milk, nasal brushes and secretions, pharyngeal swabs, skin swabs, stool, cord blood and peripheral blood (EDTA and serum). They are obtained at the defined study time points, i.e. either at day 1-3 and/or day 30 of life and/or at 6 months and/or 1 year following birth. (Created with BioRender.com).