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In contrast to gut\u2010targeting 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\n                    <jats:italic>Lactobacillaceae<\/jats:italic>\n                    strains was based on previously documented beneficial properties, up\u2010scaling and industrial production characteristics, clinical safety parameters, and potential antiviral and immunostimulatory efficacy in the URT demonstrated in this study. Using a three\u2010step selection strategy, three strains were selected and further tested in vitro antiviral assays and in formulations:\n                    <jats:italic>Lacticaseibacillus casei<\/jats:italic>\n                    AMBR2 as a promising endogenous candidate URT probiotic with previously reported barrier\u2010enhancing and anti\u2010pathogenic properties and the two well\u2010studied model strains\n                    <jats:italic>Lacticaseibacillus rhamnosus<\/jats:italic>\n                    GG and\n                    <jats:italic>Lactiplantibacillus plantarum<\/jats:italic>\n                    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\u2010229E coronavirus in co\u2010culture 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\u2010inducing 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\u2010acting live biotherapeutic strategy against respiratory viral diseases.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.14189","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T04:01:30Z","timestamp":1670212890000},"page":"99-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-7489","authenticated-orcid":false,"given":"Irina","family":"Spacova","sequence":"first","affiliation":[{"name":"Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-8515","authenticated-orcid":false,"given":"Ilke","family":"De Boeck","sequence":"additional","affiliation":[{"name":"Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Cauwenberghs","sequence":"additional","affiliation":[{"name":"Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6519-0114","authenticated-orcid":false,"given":"Lize","family":"Delanghe","sequence":"additional","affiliation":[{"name":"Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Bron","sequence":"additional","affiliation":[{"name":"Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Henkens","sequence":"additional","affiliation":[{"name":"YUN NV  Niel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix","family":"Simons","sequence":"additional","affiliation":[{"name":"YUN NV  Niel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imane","family":"Gamgami","sequence":"additional","affiliation":[{"name":"YUN NV  Niel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7898-0868","authenticated-orcid":false,"given":"Leentje","family":"Persoons","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapy, KU Leuven Department of Microbiology, Immunology and Transplantation Rega Institute  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4209-4116","authenticated-orcid":false,"given":"Ingmar","family":"Claes","sequence":"additional","affiliation":[{"name":"YUN NV  Niel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-6910","authenticated-orcid":false,"given":"Marianne F. 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