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Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections

Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory tract (URT), where the resident respiratory microbiome has an important gatekeeper function. In contrast to gut‐targeting administra...

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Autores principales: Spacova, Irina, De Boeck, Ilke, Cauwenberghs, Eline, Delanghe, Lize, Bron, Peter A., Henkens, Tim, Simons, Alix, Gamgami, Imane, Persoons, Leentje, Claes, Ingmar, van den Broek, Marianne F. L., Schols, Dominique, Delputte, Peter, Coenen, Samuel, Verhoeven, Veronique, Lebeer, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803329/
https://www.ncbi.nlm.nih.gov/pubmed/36468246
http://dx.doi.org/10.1111/1751-7915.14189
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author Spacova, Irina
De Boeck, Ilke
Cauwenberghs, Eline
Delanghe, Lize
Bron, Peter A.
Henkens, Tim
Simons, Alix
Gamgami, Imane
Persoons, Leentje
Claes, Ingmar
van den Broek, Marianne F. L.
Schols, Dominique
Delputte, Peter
Coenen, Samuel
Verhoeven, Veronique
Lebeer, Sarah
author_facet Spacova, Irina
De Boeck, Ilke
Cauwenberghs, Eline
Delanghe, Lize
Bron, Peter A.
Henkens, Tim
Simons, Alix
Gamgami, Imane
Persoons, Leentje
Claes, Ingmar
van den Broek, Marianne F. L.
Schols, Dominique
Delputte, Peter
Coenen, Samuel
Verhoeven, Veronique
Lebeer, Sarah
author_sort Spacova, Irina
collection PubMed
description Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory tract (URT), where the resident respiratory microbiome has an important gatekeeper function. In contrast to gut‐targeting administration of beneficial bacteria against respiratory viral disease, topical URT administration of probiotics is currently underexplored, especially for the prevention and/or treatment of viral infections. Here, we report the formulation of a throat spray with live lactobacilli exhibiting several in vitro mechanisms of action against respiratory viral infections, including induction of interferon regulatory pathways and direct inhibition of respiratory viruses. Rational selection of Lactobacillaceae strains was based on previously documented beneficial properties, up‐scaling and industrial production characteristics, clinical safety parameters, and potential antiviral and immunostimulatory efficacy in the URT demonstrated in this study. Using a three‐step selection strategy, three strains were selected and further tested in vitro antiviral assays and in formulations: Lacticaseibacillus casei AMBR2 as a promising endogenous candidate URT probiotic with previously reported barrier‐enhancing and anti‐pathogenic properties and the two well‐studied model strains Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum WCFS1 that display immunomodulatory capacities. The three strains and their combination significantly reduced the cytopathogenic effects of RSV, influenza A/H1N1 and B viruses, and HCoV‐229E coronavirus in co‐culture models with bacteria, virus, and host cells. Subsequently, these strains were formulated in a throat spray and human monocytes were employed to confirm the formulation process did not reduce the interferon regulatory pathway‐inducing capacity. Administration of the throat spray in healthy volunteers revealed that the lactobacilli were capable of temporary colonization of the throat in a metabolically active form. Thus, the developed spray with live lactobacilli will be further explored in the clinic as a potential broad‐acting live biotherapeutic strategy against respiratory viral diseases.
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spelling pubmed-98033292023-01-04 Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections Spacova, Irina De Boeck, Ilke Cauwenberghs, Eline Delanghe, Lize Bron, Peter A. Henkens, Tim Simons, Alix Gamgami, Imane Persoons, Leentje Claes, Ingmar van den Broek, Marianne F. L. Schols, Dominique Delputte, Peter Coenen, Samuel Verhoeven, Veronique Lebeer, Sarah Microb Biotechnol Research Articles Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory tract (URT), where the resident respiratory microbiome has an important gatekeeper function. In contrast to gut‐targeting administration of beneficial bacteria against respiratory viral disease, topical URT administration of probiotics is currently underexplored, especially for the prevention and/or treatment of viral infections. Here, we report the formulation of a throat spray with live lactobacilli exhibiting several in vitro mechanisms of action against respiratory viral infections, including induction of interferon regulatory pathways and direct inhibition of respiratory viruses. Rational selection of Lactobacillaceae strains was based on previously documented beneficial properties, up‐scaling and industrial production characteristics, clinical safety parameters, and potential antiviral and immunostimulatory efficacy in the URT demonstrated in this study. Using a three‐step selection strategy, three strains were selected and further tested in vitro antiviral assays and in formulations: Lacticaseibacillus casei AMBR2 as a promising endogenous candidate URT probiotic with previously reported barrier‐enhancing and anti‐pathogenic properties and the two well‐studied model strains Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum WCFS1 that display immunomodulatory capacities. The three strains and their combination significantly reduced the cytopathogenic effects of RSV, influenza A/H1N1 and B viruses, and HCoV‐229E coronavirus in co‐culture models with bacteria, virus, and host cells. Subsequently, these strains were formulated in a throat spray and human monocytes were employed to confirm the formulation process did not reduce the interferon regulatory pathway‐inducing capacity. Administration of the throat spray in healthy volunteers revealed that the lactobacilli were capable of temporary colonization of the throat in a metabolically active form. Thus, the developed spray with live lactobacilli will be further explored in the clinic as a potential broad‐acting live biotherapeutic strategy against respiratory viral diseases. John Wiley and Sons Inc. 2022-12-05 /pmc/articles/PMC9803329/ /pubmed/36468246 http://dx.doi.org/10.1111/1751-7915.14189 Text en © 2022 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Spacova, Irina
De Boeck, Ilke
Cauwenberghs, Eline
Delanghe, Lize
Bron, Peter A.
Henkens, Tim
Simons, Alix
Gamgami, Imane
Persoons, Leentje
Claes, Ingmar
van den Broek, Marianne F. L.
Schols, Dominique
Delputte, Peter
Coenen, Samuel
Verhoeven, Veronique
Lebeer, Sarah
Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections
title Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections
title_full Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections
title_fullStr Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections
title_full_unstemmed Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections
title_short Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections
title_sort development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803329/
https://www.ncbi.nlm.nih.gov/pubmed/36468246
http://dx.doi.org/10.1111/1751-7915.14189
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