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

Pivniouk, Vadim; Pivniouk, Oksana; DeVries, Avery; Uhrlaub, Jennifer L.; Michael, Ashley; Pivniouk, Denis; VanLinden, Sydney R.; Conway, M.; Hahn, Seongmin; Malone, Sean P.; Ezeh, Peace C.; Churko, Jared M.; Anderson, Dayna; Kraft, Monica; Nikolich‐Žugich, Janko; Vercelli, Donata

doi:10.1016/j.jaci.2021.11.019

Cited by 20 publications

(47 citation statements)

References 57 publications

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“…To confirm these findings related to the antiviral response, we investigated the effects of OM-85 in A549 cells lacking the type I response pathway (IFNAR and RIG-I knockout cells). We found that the protective role of OM-85 was completely abolished in the absence of genes related to the type I interferon response ( Figures 8G, H ), supporting the idea that the anti-viral effects demonstrated by OM-85 in various examples ( 32 – 35 , 38 , 39 , 45 , 46 ) including in this study using RSV as infective agent may be at least partially acting through modulation of the interferon response.…”

Section: Resultssupporting

confidence: 83%

“…As demonstrated, treatment with OM-85 mediated an IFNβ response in both in vivo and in vitro experiments, in sync with other studies performed with the oral route or in vitro settings ( 32 , 36 , 37 , 39 ), but this does not limit its antiviral mechanism against different viruses ( 33 , 35 , 39 ). In the present study, we found that IFNβ production in cells treated with OM–85 occurs only after virus infection.…”

Section: Discussionsupporting

confidence: 85%

“…With our previous work of an intranasal preparation of microbiota-derived acetate protecting against RSV ( 30 ), we hypothesized that several constituents from the microbial content from OM-85 could similarly mimic such protective effects against RSV. Similar protective effect with oral OM-85 were observed with in vivo studies against H1N1 and betacoronavirus, in vitro with human rhinovirus (hRV) infected lung primary epithelial cells, by reducing either SARS-CoV-2 binding proteins on epithelial cells from endobronchial biopsies, and also in live SARS-CoV-2 infection using Vero cells ( 38 , 39 ). In this study we thus aimed to investigate the effects of intranasal administration of OM-85 and its potential protective effect in RSV infected mice.…”

Section: Introductionsupporting

confidence: 59%

“…OM-85 is a bacterial lysate, and we sought to investigate the same therapeutic approach and route using this microbial product during RSV-induced disease. To determine whether OM-85 treatment modulates physiological response against RSV infection, mice were inoculated with RSV and after a period of 12 hours were treated with 1 mg of OM-85 via intranasal route, similar to the protocols used in asthma models ( 37 , 39 ). The treatment was administered daily until day 5 post-infection, which is usually the peak of the replication in the experimental models of RSV infection ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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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 IFNβ 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.

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Section: Resultssupporting

confidence: 83%

Section: Discussionsupporting

confidence: 85%

Section: Introductionsupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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“…As the first step of gene expression, the production of ACE2 mRNA has been reported to be positively correlated with the increased susceptibility to SARS-CoV-2 infection and severity of COVID-19 symptoms. 19 , 20 The alterations of ACE2 transcription and expression can be a result of genetic factors such as age 21 and race, 22 but nongenetic factors such as chemical exposure can also impact virus receptor, transcription, translation, and so forth. Work to date has not looked at how these exogenous chemicals impact virus receptor transcription or expression, which deserve further research.…”

Section: Introductionmentioning

confidence: 99%

Exogenous Chemical Exposure Increased Transcription Levels of the Host Virus Receptor Involving Coronavirus Infection

Jin

Zhang

et al. 2022

Environ. Sci. Technol.

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Virus receptors are highly involved in mediating the entrance of infectious viruses into host cells. Here, we found that typical chemical exposure caused the upregulation of virus receptor mRNA levels. Chemicals with the same structural characteristics can affect the transcription of angiotensin-converting enzyme 2 ( ACE2 ), a dominant receptor of SARS-CoV-2. Some chemicals can also regulate the transcription of ACE2 by similar regulatory mechanisms, such as multilayer biological responses and the crucial role of TATA-box binding protein associated factor 6. The abovementioned finding suggested that chemical mixtures may have a joint effect on the ACE2 mRNA level in the real scenario, where humans are exposed to numerous chemicals simultaneously in daily life. Chemically regulated virus receptor transcription was in a tissue-dependent manner, with the highest sensitivity in pulmonary epithelial cells. Therefore, in addition to genetic factors, exogenous chemical exposure can be an emerging nongenetic factor that stimulates the transcription of virus receptor abundance and may elevate the protein expression. These alterations could ultimately give rise to the susceptibility to virus infection and disease severity. This finding highlights new requirements for sufficient epidemiological data about exposomes on pathogen receptors in the host.

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Immunostimulants versus placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease

Fraser

Poole

2022

Cochrane Database of Systematic Reviews

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

Cited by 20 publications

References 57 publications

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

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

Exogenous Chemical Exposure Increased Transcription Levels of the Host Virus Receptor Involving Coronavirus Infection

Immunostimulants versus placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease

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