Bacterial Mucosal Immunotherapy with MV130 Prevents Recurrent Wheezing in Children: A Randomized, Double-Blind, Placebo-controlled Clinical Trial

Abstract

Rationale: Recurrent wheezing in children represents a severe public health concern. Wheezing attacks (WA), mainly associated with viral infections, lack effective preventive therapies. Objectives: To evaluate the efficacy and safety of mucosal sublingual immunotherapy based on whole inactivated bacteria (MV130) in preventing WA in children. Methods: A Phase 3 randomized, double-blind, placebo-controlled, parallel-group trial including a cohort of 120 children <3 years old with ⩾3 WA during the previous year was conducted. Children with a positive skin test to common aeroallergens in the area where the clinical trial was performed were excluded from the trial. Subjects received MV130 or placebo daily for 6 months. The primary endpoint was the number of WA within 1 year after the first dose comparing MV130 and placebo. Measurements and Main Results: There was a significant lower number of WA in MV130 versus the placebo group, 3.0 (interquartile range [IQR], 2.0–4.0) versus 5.0 (IQR, 3.0–7.0) ( P < 0.001). As secondary outcomes, a decrease in the duration of WA and a reduction in symptoms and medication scores in the MV130 versus placebo group were found. No adverse events were reported related to the active treatment. Conclusions: Mucosal bacterial immunotherapy with MV130 shows safety and clinical efficacy against recurrent WA in children.Clinical trial registered with www.clinicaltrials.gov (NCT 01734811).

Early Microbial–Immune Interactions and Innate Immune Training of the Respiratory System during Health and Disease

“…A proof of principle for this model has been recently provided by Nieto et al in a randomized placebo-controlled clinical trial (n = 120) [55]. In this study, mucosal sublingual immunotherapy based on whole inactivated bacteria (MV130) reduced the number of wheezing attacks (WA) and other secondary outcomes [55]. While this study supports the notion of IIT, it is still unclear regarding what the best timing for intervention should be.…”

“…In the same way that pathogenic bacteria during early life may increase the risk for respiratory disorders, exposure to protective bacteria may serve as a primary prevention. A proof of principle for this model has been recently provided by Nieto et al in a randomized placebo-controlled clinical trial (n = 120) [55]. In this study, mucosal sublingual immunotherapy based on whole inactivated bacteria (MV130) reduced the number of wheezing attacks (WA) and other secondary outcomes [55].…”

Innate Immune Training for Prevention of Recurrent Wheeze in Early Childhood

“…More comprehensive wholeanimal data is available from experimental models, which collectively point towards myeloid precursor populations in bone marrow as the primary targets for OM85-mediated IIT effects 7,15 , likely responding to multiple TLR ligands present in this agent 9 . This may account for the similarity in clinical response profiles in children evident in the recent trial results reported for OM85 13,14 and MV130 3 , both of which are derived from TLR ligand-rich mixed bacterial lysates.…”

“…This class of therapeutics is dominated by the agent OM85, derived from 8 major bacterial respiratory pathogens, which has been in widespread clinical use for over 30yrs in Europe and South America, for protection of at-risk young children and adults against sLRI and associated symptoms (reviewed 7,12 ). In addition to multiple investigations in older children and adults 12 , recent studies employing OM85 have demonstrated reduction in sLRI frequency and severity in preschool and early school age children 13 similar to that achieved with MV130 3 , and importantly have also demonstrated comparable safety/efficacy in infants preselected on the basis of high risk for atopy/asthma 14 . OM85 is also in current use in a large NIHfunded multi-centre trial (https://clinicaltrials.gov/ct2/show/NCT02148796) targeting similar outcomes.…”

Editorial: Trained Immunity-Based Vaccines

“…show how mesenchymal stem cells are able to uptake, process and retain a reservoir of the TLR ligands derived from inactivated bacteria (MV130), which can subsequently be transferred to dendritic cells. MV130 is a mucosal polybacterial preparation that induces trained immunity and prevents viral wheezing attacks in young children ( 8 ) and used in a proof of concept study in patients with hematological malignancies, showing beneficial effects in terms of infections incidence ( 9 ). The effect of the combination of a similar polybacterial preparation (MV140) used to prevent urinary tract infections with Candida albicans (V132) has been studied by Martín-Cruz et al.…”