Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85

Abstract

ObjectivesIncomplete maturation of immune regulatory functions at birth are antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the benign microbial-derived immune modulating agent OM-85 during pregnancy promotes accelerated maturation of immune regulatory networks in the developing fetal bone marrow. Here, we aimed to establish proof-of-concept that this would enhance resilience to severe early life respiratory viral infection during the neonatal period. MethodsPregnant BALB/c mice were treated orally with OM-85 during gestation and their offspring infected intranasally with a mouse-adapted rhinovirus (vMC0) at postnatal day 2. We then assessed clinical course, lung viral titres and lung immune parameters to determine whether offspring from OM-85 treated mothers demonstrate enhanced immune protection against neonatal vMC0 infection. ResultsOffspring from OM-85 treated mothers display enhanced capacity to clear an otherwise lethal respiratory viral infection during the neonatal period, with a concomitant reduction in the exaggerated nature of the ensuing immune response. These treatment effects were associated with accelerated postnatal myeloid cell seeding of neonatal lungs and enhanced expression of microbial sensing receptors in lung tissues, coupled in particular with enhanced capacity to rapidly expand and maintain networks of lung dendritic cells expressing function-associated markers crucial for maintenance of local immune homeostasis in the face of pathogen challenge. ConclusionMaternal OM-85 treatment may represent a novel therapeutic strategy to reduce the burden, and potential long-term sequlae, of severe neonatal respiratory viral infection by accelerating development of innate immune competence.