@article{99bfaec788dc4107afb014c5b71719a2,
title = "Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis",
abstract = "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.",
keywords = "Bacterial lysate, OM-85, adaptive immunity, airway compartment, allergic inflammation, asthma, innate immunity, intranasal route, microbial interventions",
author = "Vadim Pivniouk and Gimenes-Junior, {Joao A.} and Peace Ezeh and Ashley Michael and Oksana Pivniouk and Seongmin Hahn and VanLinden, {Sydney R.} and Malone, {Sean P.} and Amir Abidov and Dayna Anderson and Justyna Gozdz and Avery DeVries and Fernando Martinez and Christian Pasquali and Donata Vercelli",
note = "Funding Information: We thank Dean Billheimer, Department of Epidemiology and Biostatistics, College of Public Health and Statistical Consulting, The BIO5 Institute, University of Arizona, for expert statistical advice. This work was funded in part by a research grant provided by OM Pharma SA to The University of Arizona. Support was also provided by postdoctoral fellowships from T32 ES007091 and The BIO5 Institute (to A.D.V.), a predoctoral T32 HL007249 fellowship (to S.R.V.L.), and the National Institutes of Health (P01AI148104 and R21AI144722 to D.V.). Disclosure of potential conflict of interest: D. Vercelli, C. Pasquali, V. Pivniouk, and F. D. Martinez are inventors in PCT/EP2019/074562, “Method of Treating and/or Preventing Asthma, Asthma Exacerbations, Allergic Asthma and/or Associated Conditions with Microbiota Related to Respiratory Disorders.” S. R. VanLinden reports receipt of a fellowship from a National Institutes of Health (NIH) predoctoral training grant outside the submitted work. A. DeVries reports grants from NIH (predoctoral and postdoctoral training grants) outside the submitted work. F. D. Martinez reports grants from NIH/National Heart, Lung, and Blood Institute, grants from NIH/National Institute of Environmental Health Sciences, grants from NIH/National Institute of Allergy and Infectious Diseases (NIAID), grants from NIH/Office of Director, and grants from Johnson & Johnson, outside the submitted work. C. Pasquali is an employee of OM Pharma. D. Vercelli reports grants from NIAID outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: This work was funded in part by a research grant provided by OM Pharma SA to The University of Arizona. Support was also provided by postdoctoral fellowships from T32 ES007091 and The BIO5 Institute (to A.D.V.), a predoctoral T32 HL007249 fellowship (to S.R.V.L.), and the National Institutes of Health (P01AI148104 and R21AI144722 to D.V.). Funding Information: Disclosure of potential conflict of interest: D. Vercelli, C. Pasquali, V. Pivniouk, and F. D. Martinez are inventors in PCT/EP2019/074562, “Method of Treating and/or Preventing Asthma, Asthma Exacerbations, Allergic Asthma and/or Associated Conditions with Microbiota Related to Respiratory Disorders.” S. R. VanLinden reports receipt of a fellowship from a National Institutes of Health (NIH) predoctoral training grant outside the submitted work. A. DeVries reports grants from NIH (predoctoral and postdoctoral training grants) outside the submitted work. F. D. Martinez reports grants from NIH/National Heart, Lung, and Blood Institute, grants from NIH/National Institute of Environmental Health Sciences, grants from NIH/National Institute of Allergy and Infectious Diseases (NIAID), grants from NIH/Office of Director, and grants from Johnson & Johnson, outside the submitted work. C. Pasquali is an employee of OM Pharma. D. Vercelli reports grants from NIAID outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: {\textcopyright} 2021 American Academy of Allergy, Asthma & Immunology",
year = "2022",
month = mar,
doi = "10.1016/j.jaci.2021.09.013",
language = "English (US)",
volume = "149",
pages = "943--956",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",
}