Oral Bacterial Lysate OM-85: Advances in Pharmacology and Therapeutics.

Background: Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1 helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Methods: Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. Results: New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient's characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification). Conclusion: OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.

A critical analysis of the effect of OM-85 for the prevention of recurrent respiratory tract infections or wheezing/asthma from systematic reviews with meta-analysis.

Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.

Preventive effects of prenatal administration of OM-85/BV on asthma and respiratory infection risk in the offspring: A review of animal models.

Asthma is the most common chronic disease in childhood affecting the daily lives of many patients despite current treatment regimens. Therefore, the need for new therapeutic approaches is evident, where a primary prevention strategy is the ultimate goal. Studies of children born to mothers in farming environments have shown a lower risk of respiratory infections and asthma development. Already at birth, these newborns have demonstrated accelerated maturation and upregulation of host defense immune functions suggesting a prenatal transplacental training of the innate immune system through maternal microbial exposure. This mechanism could possibly be utilized to help prevent both respiratory infections and asthma in young children. Human studies exploring the potential preventative effects of pregnancy bacterial lysate treatment on asthma and respiratory infections are lacking, however, this has been studied in experimental studies using mice through administrations of the bacterial lysate OM-85. This review will present the current literature on the immunomodulatory effects relevant for respiratory infections and asthma in the offspring of mice treated with OM-85 throughout pregnancy. Further, the review will discuss the cellular and molecular mechanisms behind these effects. In conclusion, we found promising results of an accelerated immune competence and improved resistance to airway challenges as a result of prenatal bacterial lysate treatment that may pave the way for implementing this in human trials to prevent asthma and respiratory infections.

[Efficacy and safety of bacterial lysate OM-85 in the treatment of uncomplicated acute respiratory infections: a double-blind, placebo-controlled, multicenter, randomized trial].

AIM: To evaluate the efficacy and safety of OM-85 in the treatment of uncomplicated acute respiratory infections (ARI) in adults. MATERIALS AND METHODS: A double-blind, placebo-controlled, multicenter, randomized trial included 556 patients (18-60 years old) with mild and moderate ARI and negative results of polymerase chain reaction analysis for SARS-CoV-2 RNA and rapid test for influenza A and B viruses. Patients were randomized into two groups: in the first group (n=278), patients received OM-85 (Broncho-munal®) one capsule 7 mg/day for 10 days, while the second group (n=278) was treated with placebo in the same regimen. The primary endpoint was the dynamics of the severity of symptoms over 3, 5, 7 and 10 days of treatment according to the 21-item Wisconsin Upper Respiratory Symptom Survey (WURSS-21), which was assessed by the area under the curve. Secondary efficacy criteria were the dynamics of the severity of symptoms according to the Common Cold Questionnaire (CCQ), the time to the resolution of symptoms according to WURSS-21 and CCQ, the proportion of patients with body temperature below 37°C on each day of treatment, frequency of the need for systemic antibacterial therapy. RESULTS: The superiority of OM-85 over placebo by primary endpoint was observed on the 5th, 7th and 10th days of treatment. OM-85 efficacy has also been proven by secondary criteria. OM-85 shortened the time until the symptoms of ARI resolved according to the WURSS-21 and CCQ, increased the proportion of patients with body temperature below 37°C by 2-9 days. The time needed to resolve the symptoms of disease in 20% of patients according to WURSS-21 was 7 and 9 days in patients taking OM-85 and placebo, respectively. Bacterial lysate increased the probability of complete disappearance of symptoms according to CCQ by 45.7% compared to placebo. The analysis of the frequency and severity of adverse events, laboratory tests, physical and instrumental examination results during treatment confirmed the good tolerability and safety of OM-85. CONCLUSION: The study confirmed the efficacy and safety of OM-85 in the complex treatment of ARI in adults.

Effect of Broncho-Vaxom (OM-85) on the frequency of chronic obstructive pulmonary disease (COPD) exacerbations.

BACKGROUND: Efforts have been made to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations using a variety of measures. Broncho-Vaxom (BV) is an immunomodulating agent that has shown potential benefit by balancing between immune stimulation and regulation in patients with COPD. In this study, we evaluated the clinical efficacy of BV for reducing the risk of COPD exacerbations. METHODS: This study was based on the Korean National Health Insurance database, which contains reimbursement information for almost the entire population of South Korea. We extracted data from 2016 to 2019 for patients started on BV during 2017-2018. We collected baseline data on demographics, comorbidities, inhaler use, hospital type, and insurance type 1 year before starting BV. We also analyzed exacerbation history, starting from the year before BV initiation. RESULTS: In total, 238 patients were enrolled in this study. Their mean age was 69.2 ± 9.14 years, 79.8% were male, and 45% experienced at least one exacerbation. BV reduced the risk of moderate (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.38-0.91) and moderate-to-severe exacerbations compared to pre- and post-BV (OR = 0.571, 95% CI: 0.37-0.89). BV use also reduced the incidence of moderate and moderate-to-severe exacerbations (incidence rate ratio [IRR] = 0.75, p = 0.03; and IRR = 0.77, p = 0.03, respectively). The use of BV was significantly delayed moderate exacerbations (hazard ratio = 0.68, p = 0.02), but not with moderate-to-severe or severe exacerbations. CONCLUSION: The use of BV was associated with fewer moderate and moderate-to-severe exacerbations. Additionally, BV was associated with a delay in moderate COPD exacerbations.

Efficacy of OM-85 in Recurrent Respiratory Tract Infections.

BACKGROUND: In older patients, prevention of acute respiratory tract infections (RTIs) is challenging. Experimental studies have consistently underlined an immune-potentiating effect of the bacterial lysates product OM85, on both cellular and humoral responses. OBJECTIVE: This work aimed to assess the potential efficacy of OM-85 for RTIs' prevention in older individuals. METHODS: This explorative longitudinal study included 24 patients aged 65 years or older recruited in the GeroCovid Observational Study- home and outpatient care cohort. For the study purposes, we included 8 patients treated with OM-85 from December 2020 to June 2021 (group A), and a control group of 16 patients, matched for sex and age, who did not receive bacterial lysates (group B). RTIs were recorded from the participants' medical documentation in an e-registry from March 2020 to December 2021. RESULTS: In 2020, group A experienced a total of 8 RTIs, which affected 6 out of 8 patients (75%); group B reported 21 RTIs, with at least one event in 11 out of 16 patients (68.7%). In 2021, RTIs affected 2 out of 8 patients (25%) in group A (p < 0.02), and 13 out of 16 patients (81.2%) in group B (within this group, 5 patients had two RTIs). The RTIs' cumulative incidence over the observation period significantly differed between groups (66.7% in group A vs. 24.3% in group B; p < 0.002), as well as the decrease in RTIs frequency from 2020 to 2021. No patients in group A were affected by COVID-19 during the observation period, while among controls, two patients had SARS-CoV-2 infection, notwithstanding three doses of vaccine. CONCLUSION: This study suggests that bacterial lysates may provide clinical benefits for preventing RTIs. Additional research involving larger cohorts is required to verify the effectiveness of OM-85 in preventing RTIs in older adults.

The OM-85 bacterial lysate: a new tool against SARS-CoV-2?

The emergence of SARS-CoV-2, a novel coronavirus, caused the global Coronavirus disease of 2019 (COVID-19) pandemic. Because SARS-CoV-2 mutates rapidly, vaccines that induce immune responses against viral components critical for target cell infection strongly mitigate but do not abrogate viral spread, and disease rates remain high worldwide. Complementary treatments are therefore needed to reduce the frequency and/or severity of SARS-CoV-2 infections. OM-85, a standardized lysate of 21 bacterial strains often found in the human airways, has immuno-modulatory properties and is widely used empirically in Europe, South America and Asia for the prophylaxis of recurrent upper airway infections in adults and children, with excellent safety profiles. In vitro studies from our laboratory recently demonstrated that OM-85 inhibits SARS-CoV-2 epithelial cell infection by downregulating SARS-CoV-2 receptor expression, raising the possibility that this bacterial extract might eventually complement the current COVID-19 therapeutic toolkit. Here we discuss how our results and those from other groups are fostering progress in this emerging field of research.

Can bacterial lysates be useful in prevention of viral respiratory infections in childhood? The results of experimental OM-85 studies.

Respiratory tract infections (RTI) are mainly viral in origin and among the leading cause of childhood morbidity globally. Associated wheezing illness and asthma are still a clear unmet medical need. Despite the continuous progress in understanding the processes involved in their pathogenesis, preventive measures and treatments failed to demonstrate any significant disease-modifying effect. However, in the last decades it was understood that early-life exposure to microbes, may reduce the risk of infectious and allergic disorders, increasing the immune response efficacy. These results suggested that treatment with bacterial lysates (BLs) acting on gut microbiota, could promote a heterologous immunomodulation useful in the prevention of recurrent RTIs and of wheezing inception and persistence. This hypothesis has been supported by clinical and experimental studies showing the reduction of RTI frequency and severity in childhood after oral BL prophylaxis and elucidating the involved mechanisms. OM-85 is the product whose anti-viral effects have been most extensively studied in vitro, animal, and human cell studies and in translational animal infection/disease models. The results of the latter studies, describing the potential immune training-based activities of such BL, leading to the protection against respiratory viruses, will be reported. In response to human rhinovirus, influenza virus, respiratory syncytial virus and severe acute respiratory coronavirus-2, OM-85 was effective in modulating the structure and the functions of a large numbers of airways epithelial and immune cells, when administered both orally and intranasally.

Microbiota profiles in pre-school children with respiratory infections: Modifications induced by the oral bacterial lysate OM-85.

To describe microbiota profiles considering potential influencing factors in pre-school children with recurrent respiratory tract infections (rRTIs) and to evaluate microbiota changes associated with oral bacterial lysate OM-85 treatment, we analyzed gut and nasopharynx (NP) microbiota composition in patients included in the OM-85-pediatric rRTIs (OMPeR) clinical trial (https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-002705-19/IT). Relative percentage abundance was used to describe microbiota profiles in all the available biological specimens, grouped by age, atopy, and rRTIs both at inclusion (T0) and at the end of the study, after treatment with OM-85 or placebo (T1). At T0, Firmicutes and Bacteriodetes were the predominant genera in gut and Proteobacteria, Firmicutes, and Actinobacteria were the predominant genera in NP samples. Gut microbiota relative composition differed with age (<2 vs. ≥2 years) for Firmicutes, Proteobacteria, Actinobacteria (phyla) and Bifidobacterium, Ruminococcus, Lachnospiraceae (genera) (p < 0.05). Moraxella was more enriched in the NP of patients with a history of up to three RTIs. Intra-group changes in relative percentage abundance were described only for patients with gut and NP microbiota analysis available at both T0 and T1 for each study arm. In this preliminary analysis, the gut microbiota seemed more stable over the 6-month study in the OM-85 group, whose mean age was lower, as compared to the placebo group (p = 0.004). In this latter group, the relative abundance of Bacteroides decreased significantly in children ≥2 years. Some longitudinal significant differences in genera relative abundance were also detected in children of ≥2 years for NP Actinobacteria, Haemophilus, and Corynebacterium in the placebo group only. Due to the small number of patients in the different sub-populations, we could not identify significant differences in the clinical outcome and therefore no associations with microbiota changes were searched. The use of bacterial lysates might play a role in microbiota rearrangement, but further data and advanced analysis are needed to prove this in less heterogeneous populations with higher numbers of samples considering the multiple influencing factors such as delivery method, age, environment, diet, antibiotic use, and type of infections to ultimately show any associations with prevention of rRTIs.

Expert consensus on the role of OM-85 in the management of recurrent respiratory infections: A Delphi study.

Recurrent infections of upper and lower respiratory tract have an important clinical and economic impact, which can be reduced through appropriate preventive measures, including the use of immunomodulating agents, such as OM-85, which proved to be effective and safe in both adults and children. Although OM-85 can be useful for the prevention of respiratory tract infections, it is still underused in clinical practice. In order to evaluate the level of awareness of the disease burden of recurrent respiratory infections in adults and children and to assess the level of agreement on the prophylactic and therapeutic approach to the disease, including the use of immunomodulants, a Delphi study was performed. A board of six experts in the field of respiratory infections was appointed to elaborate a series of statements covering four main topics (disease, prevention, OM-85, and future strategies), which were thereafter voted by a panel of 30 experts. Results showed that prevention is unanimously recognized as the most important intervention to reduce disease burden, and the use of immunomodulation to improve the effectiveness of vaccination is gaining increasing favor among clinicians. In this respect, OM-85 is recognized as the most studied immunomodulating agent currently available, whose efficacy and safety make it a valuable tool to optimize the management of recurrent respiratory infections in both adults and children. In particular, the combined use of OM-85 and influenza vaccine was recognized as an effective and safe approach to improve the current prevention strategies in order to reduce the burden of recurrent respiratory infections.

Investigational approaches for unmet need in severe asthma.

INTRODUCTION: Molecular antibodies (mAb) targeting inflammatory mediators are effective in T2-high asthma. The recent approval of Tezepelumab presents a novel mAb therapeutic option for those with T2-low asthma. AREAS COVERED: We discuss a number of clinical problems pertinent to severe asthma that are less responsive to current therapies, such as persistent airflow obstruction and airway hyperresponsiveness. We discuss selected investigational approaches, including a number of candidate therapies under investigation in two adaptive platform trials currently in progress, with particular reference to this unmet need, as well as their potential in phenotypes such as neutrophilic asthma and obese asthma, which may or may not overlap with a T2-high phenotype. EXPERT OPINION: The application of discrete targeting approaches to T2-low molecular phenotypes, including those phenotypes in which inflammation may not arise within the airway, has yielded variable results to date. Endotypes associated with T2-low asthma are likely to be diverse but await validation. Investigational therapeutic approaches must, likewise, be diverse if the goal of remission is to become attainable for all those living with asthma.

A Meta-Analysis on the Efficacy and Safety of Bacterial Lysates in Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common and frequently encountered disease of respiratory apparatus and is vulnerable to infection. Increasing studies reveal that bacterial lysates play an encouraging role in preventing exacerbations in these patients. We here investigated the efficacy and safety of bacterial lysates in COPD. Methods: We performed systematic research on PubMed, EMBASE, the Cochrane Library (CENTRAL), and Web of Science by using the keywords and their synonyms for studies published before January 11, 2022. Two researchers screened the studies of literature independently according to the inclusion and exclusion criteria and extracted data from the included studies. Another two researchers assessed the risk of bias of each included using the Cochrane risk-of-bias tool. Meta-analysis was conducted using R (version 4.1.1, The R Foundation for Statistical Computing) and Review Manager (version 5.4.0, The Cochrane Collaboration). Results: A total of 12 studies were included in this meta-analysis, and the pooled results showed that bacterial lysates were effective to reduce exacerbation rate (overall: relative risk [RR] = 0.83, 95% confidence interval [CI] 0.72-0.96; alkaline bacterial lysate subgroup [OM-85]: RR = 0.87, 95% CI 0.77-0.98; mechanical bacterial lysate subgroup [Ismigen]: RR = 0.70, 95% CI 0.41-1.20) and mean number of exacerbations (overall: MD = -0.42, 95% CI -0.75 to -0.08; alkaline bacterial lysate subgroup [OM-85]: MD = -0.72, 95% CI -1.35 to -0.09; mechanical bacterial lysate subgroup [Ismigen]: MD = -0.02, 95% CI -0.21 to 0.17). Bacterial lysates were also found beneficial in alleviating symptoms. The side effects were acceptable and slight. Conclusion: Bacterial lysates can benefit patients with COPD by reducing exacerbations and alleviating symptoms. OM-85 is the preferable product based on the existing evidence. Further studies are needed to validate these findings. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022299420].

Airway Administration of Bacterial Lysate OM-85 Protects Mice Against Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is a seasonal pathogen responsible for the highest percentage of viral bronchiolitis in pediatric patients. There are currently no vaccine available and therapeutic methods to mitigate the severity of RSV bronchiolitis are limited. OM-85, an oral standardized bacterial lysate isolated from human respiratory strains and widely used to prevent recurrent infections and/or exacerbations in populations at risk, has been shown to be effective and safe in children and adults. Here, we demonstrate that airway administration of OM-85 in Balb/c mice prior to infection prevents RSV-induced disease, resulting in inhibition of viral replication associated with less perivascular and peribronchial inflammation in the lungs. These protective effects are dose and time-dependent with complete protection using 1mg dose of OM-85 only four times intranasally. Mechanistic insights using this topical route in the airways revealed increased alveolar macrophages, a selective set of tolerogenic DCs, Treg and Th1 expansion in the lung, even in the absence of infection, contributing to a better Th1/Th2 balance and preventing ILC2 recruitment in the airways and associated inflammatory sequelae. OM-85 preventive treatment also improved antiviral response by increasing IFNß and its responsive genes in the lung. In vitro, OM-85 protects against RSV infection in a type I interferon pathway. Our animal model data suggest that intranasal use of OM-85 should be considered as a potential prophylactic product to prevent RSV bronchiolitis once human studies confirm these findings.

The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression.

BACKGROUND: Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions. OBJECTIVES: We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2. METHODS: ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung, and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro. RESULTS: OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation. CONCLUSIONS: OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of coronavirus disease 2019.

Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis.

BACKGROUND: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections and a clinical trial is testing its ability to prevent asthma in high-risk children. We previously showed that intranasal administration of microbial products from farm environments abrogates experimental allergic asthma. OBJECTIVES: We sought to investigate whether direct administration of OM-85 to the airway compartment protects against experimental allergic asthma; and to identify protective cellular and molecular mechanisms activated through this natural route. METHODS: Different strains of mice sensitized and challenged with ovalbumin or Alternaria received OM-85 intranasally, and cardinal cellular and molecular asthma phenotypes were measured. Airway transfer experiments assessed whether OM-85-treated dendritic cells protect allergen-sensitized, OM-85-naive mice against asthma. RESULTS: Airway OM-85 administration suppressed allergic asthma in all models acting on multiple innate and adaptive immune targets: the airway epithelium/IL-33/ILC2 axis, lung allergen-induced type 2 responses, and dendritic cells whose Myd88/Trif-dependent tolerogenic reprogramming was sufficient to transfer OM-85-induced asthma protection. CONCLUSIONS: We provide the first demonstration that administering a standardized bacterial lysate to the airway compartment protects from experimental allergic asthma by engaging multiple immune pathways. Because protection required a cumulative dose 27- to 46-fold lower than the one reportedly active through the oral route, the efficacy of intranasal OM-85 administration may reflect its direct access to the airway mucosal networks controlling the initiation and development of allergic asthma.

OM-85 Broncho-Vaxom®, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells.

In clinical studies, OM-85 Broncho-Vaxom®, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 on the expression of S-protein binding proteins by human bronchial epithelial cells. Human bronchial epithelial cells were treated with OM-85 over 5 days. The expression of SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2), transmembrane protease serine subtype 2 (TMPRSS2), dipeptidyl peptidase-4 (DPP4), and a disintegrin and metalloprotease 17 (ADAM17) were determined by Western blotting and quantitative RT-PCR. Soluble (s)ACE2, heparan sulfate, heparanase, and hyaluronic acid were assessed by ELISA. OM-85 significantly reduced the expression of ACE2 (p < 0.001), TMPRSS2 (p < 0.001), DPP4 (p < 0.005), and cellular heparan sulfate (p < 0.01), while ADAM17 (p < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 (p < 0.05), hyaluronic acid (p < 0.002), and hyaluronan synthase 1 (p < 0.01). Consequently, the infection by a SARS-CoV-2 spike protein pseudo-typed lentivirus was reduced in cells pretreated with OM-85. All effects of OM-85 were concentration- and time-dependent. The results suggest that OM-85 might reduce the binding of SARS-CoV-2 S-protein to epithelial cells by modification of host cell membrane proteins and specific glycosaminoglycans. Thus, OM-85 might be considered as an add-on for COVID-19 therapy.

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

OBJECTIVES: Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways. Here, we aimed to provide proof of concept for a novel solution to reduce the burden and potential long-term sequelae of severe early-life respiratory viral infection through maternal oral treatment during pregnancy with OM-85, already in widespread human clinical use. METHODS: In this study, we performed flow cytometry and targeted gene expression (RT-qPCR) analysis on lungs from neonatal offspring whose mothers received oral OM-85 treatment during pregnancy. We next determined whether neonatal offspring from OM-85 treated mothers demonstrate enhanced protection against lethal lower respiratory infection with mouse-adapted rhinovirus (vMC0), and associated lung immune changes. RESULTS: Offspring from mothers treated with OM-85 during pregnancy display accelerated postnatal seeding of lung myeloid populations demonstrating upregulation of function-associated markers. Offspring from OM-85 mothers additionally exhibit enhanced expression of TLR4/7 and the IL-1ß/NLRP3 inflammasome complex within the lung. These treatment effects were associated with enhanced capacity to clear an otherwise lethal respiratory viral infection during the neonatal period, with concomitant regulation of viral-induced IFN response intensity. CONCLUSION: These results demonstrate that maternal OM-85 treatment protects offspring against lethal neonatal respiratory viral infection by accelerating development of innate immune mechanisms crucial for maintenance of local immune homeostasis in the face of pathogen challenge.

Use of the Bacterial Lysate OM-85 in the Paediatric Population in Italy: A Retrospective Cohort Study.

BACKGROUND: In Italy, the bacterial lysate OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®) is registered for the prophylaxis of recurrent respiratory tract infections (RTIs) in adults and children above one year of age, but there are limited data on its use in the paediatric population. We aim to estimate the impact of OM-85 treatment on RTIs and antibiotic prescriptions in children. METHODS: This study included children aged 1 to 14 years enrolled in Pedianet, a paediatric general practice research database, from January 2007 to June 2017, having at least one prescription of OM-85. Children with less than 12 months of follow-up before (PRE period) and after (POST period) the OM-85 prescription were excluded. The frequency of antibiotic prescriptions and the frequency of RTI episodes in the PRE and POST periods were compared through the post-hoc test. Subgroup analysis was performed in children with recurrent RTIs. RESULTS: 1091 children received 1382 OM-85 prescriptions for a total follow-up of 619,525.5 person-years. Overall, antibiotic prescriptions decreased from a mean of 2.8 (SD (standard deviation) 2.7) prescriptions in the PRE period to a mean of 2.2 (SD 2.6) prescriptions in the POST period (p < 0.0001). RTIs decreased from a mean of 3.4 (SD 2.9) episodes in the PRE period to a mean of 2.5 (SD 2.6) episodes in the POST period (p < 0.0001). No change in antibiotic class was noted, and co-amoxiclav remained the preferred therapy in 28% of cases, followed by amoxicillin. These results were confirmed among children with recurrent RTIs. CONCLUSIONS: OM-85 is effective in preventing both antibiotic prescriptions and RTIs in children.

Effect of OM-85 BV on reducing bronchiectasis exacerbation in Chinese patients: the iPROBE study.

BACKGROUND: Bronchiectasis is characterized by recurrent infectious exacerbations. No existing data inform preventive strategy for exacerbations beyond chronic macrolides. OM-85 BV, an immunostimulant, has been shown to prevent recurrent respiratory infections. We initiated this 1-year, multi-centered, double-blind, and controlled trial to investigate the PReventive effect of OM-85 BV on Bronchiectasis Exacerbations in Chinese patients (iPROBE). METHODS: Patients with bronchiectasis aged 18 to 75 years, having at least one exacerbation in the past year, were randomized to receive, in addition to any respiratory medications, two courses of 7 mg of OM-85 BV or matching placebo (one capsule orally per day for 10 days a month) for 3 consecutive months, followed by 3 months without treatment. The primary outcomes included the number of acute infectious exacerbations and the time to first exacerbation. Secondary endpoints included patient-reported respiratory outcomes. Safety measures were also assessed. RESULTS: Among the 196 participants, 99 were in the OM-85 BV group and 97 in the placebo group. At week 52, the mean number of acute exacerbations per patient was equal to 0.98 and 0.75, respectively, in the two groups (P=0.14). Difference in the time to first pulmonary exacerbation was not statistically significant (P=0.11). There was no statistically significant difference in any secondary end-points. The safety profile in the two arms was good and the majority of adverse events were mild. CONCLUSIONS: OM-85 BV did not demonstrate protection in decreasing pulmonary exacerbations of bronchiectasis in this trial performed in Chinese patients. It had good safety profile.

[The efficacy of OM85-BV in the treatment of recurrent upper respiratory tract infection with adenoid hypertrophy and the preliminary exploration of potential therapeutic mechanism].

Objective:To observe the efficacy of OM85-BV in the treatment of recurrent upper respiratory tract infection with adenoid hypertrophy and to explore its possible mechanism. Method:Four hundred and forty-eight children with recurrent upper respiratory tract infection and adenoid hypertrophy were collected. Three hundred and twenty-six patients in the control group were treated with conventional drugs, and one hundred and twenty-two patients in the observation group were treated with OM85-BV+conventional drugs, and the treatment lasted 12 weeks. The sleep obstructive symptoms of adenoid hypertrophy were scored according to OSA-18 before and after the treatment respectively（0, 6, 12 weeks）. The symptoms scores and effective rate of treatment between the study and the control group were compared. The patients in the control group and the observation group who were unresponsive to drug treatment received surgery after 12 weeks of drug treatment. The levels of serum IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ and IgE, the ratio of serum CD3, CD4, CD8 in lymphocytes and the ratio of CD4/CD8 were compared between the study and the control group before operation. The levels of HBD-2, IFN-γ, IL-4, IL-6 cytokines in the adenoid were compared between the control group and the observation group. The expression and distribution of adenoid HBD-2, IFN-γ, IL-4, IL-6 were compared between the control group and the observation group. Result:After 12 weeks of treatment, the total effective rate of the observation group was significantly higher than that of the control group, and the improvement of sleep respiratory obstruction symptoms of children with recurrent upper respiratory tract infection and adenoid hypertrophy was also much better than that of the control group. The serum IFN-γ of the observation group was significantly higher than that of the control group, and there was no significant difference in serum IL-2, IL-4, IL-6, IL-10, TNF, IgE between the observation group and the control group. There was no significant difference in serum CD3, CD4, CD8 and CD4/CD8 between the observation group and the control group. In the observation group, the adenoid HBD-2 was significantly higher but IL-4, IFN-γ were significantly lower than that in the control group, and IL-6 had no significant difference compared with the control group. Conclusion:OM85-BV can significantly improve the sleep apnea symptoms but can not rise the level of immune lymphocytes in children with adenoid hypertrophy and recurrent upper respiratory tract infection.OM85-BV can improve the Th1 immune response, enhancing the ability of human body to fight against pathogens and induce the release of HBD-2, increasing the resistance to microorganisms, reducing the bacteria aggregation, weakening the local inflammatory response in adenoids.