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Evolution of the antibody repertoires to rhinoviruses and house dust mites in relation to asthma inception and persistence: A high-resolution analysis in humans and mice

Rhinovirus infections and allergy to house dust mites are the main trigger of pre-school wheezing and acute exacerbations of asthma. The Rhinovirus (RV, genus Enterovirus) is a wide and diverse virus group with 12 different species, of which RV-A, RV-B, and RV-C are linked to the respiratory tract. To design immune preventive strategies (e.g. vaccine production) it is necessary to identify those RV serotypes that are associated with severe wheezing illness and asthma exacerbations. House dust mites (HDM) are ubiquitous allergens inducing atopic sensitization, allergic rhinitis, and asthma. Children that are sensitized and exposed to HDM allergens are predisposed to more severe respiratory symptoms once infected by respiratory viruses like RV. However, the predictive value and determinants of antibody responses to B-cell epitopes of RV have never been examined so far in birth cohort studies. Moreover, little is known about the mutual influence and synergic clinical relevance of the antibody responses to rhinoviruses and airborne allergens.

Based on the hypotheses raised by the epidemiological, observational, and retrospective analyses in participants of the MAS birth cohort (Multicenter Allergy Study) we have the following aims:

• Experimental verification of the MAS birth cohort hypotheses in mouse models of respiratory virus infections and allergen-induced experimental asthma.
• Investigation of the evolution of antibody responses to respiratory viruses, its determinants, and its clinical relevance.
• Identification of interactions and reciprocal influences between the antibody responses to viruses and those to airborne allergens.
• Identification of early serological biomarkers predicting the clinical evolution and persistence of wheezing disorders in early childhood