Protection against maternal infection-associated fetal growth restriction - proof-of-concept with a microbial-derived immunomodulator OM85: safety and efficacy data
Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Employing mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85TM), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial LPS or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress, notably high levels of RANTES, MIP-1a, CCL2, IL-8 and G-CSF in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses conducted in parallel employing RNASeq revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF-, IL1-, and IFNg-driven that drive production of these pro-inflammatory cytokines, without constraining Type1-IFN-associated networks central to first-line anti-microbial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.\n\nDisclosureThis study was funded principally by Nation Health and Medical Research Council (NHMRC) of Australia with supplementary support provided by OM Pharma (Geneva, Switzerland).\n\nCP is an employee of OM Pharma (Vifor Pharma). The other authors declare that they have no conflict of interest.