Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections. Issue 1 (5th December 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Microbial biotechnology. Volume 16:Issue 1(2023)
• Page Start: 99
• Page End: 115
• Publication Date: 2022-12-05
• Subjects: Microbial biotechnology -- Periodicals; Biotechnology; Microbiology; 660.62
• DOI: 10.1111/1751-7915.14189
• Languages: English
• ISSNs: 1751-7915

Abstract

Abstract: 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. Abstract : In this study we explored direct antiviral and interferon pathway‐inducing mechanisms of beneficial lactobacilli in vitro, and, based on these experimental findings, developed a throat spray with potential action against viral disease containing three beneficial lactobacilli isolated from healthy humans. The lactobacilli were formulated in an easy‐to‐use throat spray, which was tested in healthy volunteers to validate its application in real‐life settings. The spray could be a stepping stone for prevention and treatment of viral respiratory tract infections with locally applied beneficial bacteria, and will be further evaluated in primary care patients with viral respiratory tract infections.