{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T21:23:24Z","timestamp":1748726604519,"version":"3.40.5"},"reference-count":34,"publisher":"Microbiology Society","issue":"7","funder":[{"DOI":"10.13039\/501100006041","name":"Innovate UK","doi-asserted-by":"crossref","award":["IUK 72725"],"award-info":[{"award-number":["IUK 72725"]}],"id":[{"id":"10.13039\/501100006041","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,4]]},"abstract":"<jats:p>\n                  <jats:bold>Introduction.<\/jats:bold> Administered nasally, spores of the Gram-positive bacterium <jats:italic>Bacillus subtilis<\/jats:italic> have been shown to be able to induce innate immunity sufficient to confer protection to influenza and respiratory syncytial virus.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Hypothesis.<\/jats:bold> Although members of the aerobiome, intranasal delivery of high numbers of live spores carries potential safety issues.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Aim.<\/jats:bold> To address the potential safety risk of using live spores, we assessed the safety of spores that had been completely inactivated using heat sterilization.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methodology.<\/jats:bold> Using autoclaved, and therefore killed, spores of a generally recognized as safe-notified <jats:italic>B. subtilis<\/jats:italic> strain (DSM 32444), safety was assessed <jats:italic>in vitro<\/jats:italic> (biotype, genome and cell based cytoxicity) and <jats:italic>in vivo<\/jats:italic>, using intranasal administration in rodent models and lastly in human volunteers.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results.<\/jats:bold> Using a 15-day, repeat-dose, regimen in a rodent model, no indication of toxicity was observed. In a registered human study (NCT05984004), a formulated preparation of inactivated DSM 32444 spores referred to as SPEROVID was developed, and tolerance in human volunteers was assessed following 7\u2009days of nasal dosing (2\u20134 times\/day).<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion.<\/jats:bold> Our study demonstrated that in humans an intranasal dose of up to 3\u00d710<jats:sup>8<\/jats:sup> killed spores was safe and well tolerated.<\/jats:p>","DOI":"10.1099\/jmm.0.001845","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T12:17:56Z","timestamp":1720095476000},"source":"Crossref","is-referenced-by-count":3,"title":["Intranasal administration of DSM 32444 Bacillus subtilis spores: safety and tolerability"],"prefix":"10.1099","volume":"73","author":[{"given":"Yen-Linh Thi","family":"Ho","sequence":"first","affiliation":[{"name":"Huro Biotech JSC, Lot A1-8, VL3 Road, Vinh Loc 2 Industrial Park, Long Hiep Commune, Ben Luc District, Long An Province, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Hynes","sequence":"additional","affiliation":[{"name":"Destiny Pharma plc., Sussex Innovation Centre, Science Park Square, Falmer, Brighton, BN1 9SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Martina","sequence":"additional","affiliation":[{"name":"Destiny Pharma plc., Sussex Innovation Centre, Science Park Square, Falmer, Brighton, BN1 9SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bill","family":"Love","sequence":"additional","affiliation":[{"name":"Destiny Pharma plc., Sussex Innovation Centre, Science Park Square, Falmer, Brighton, BN1 9SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ed","family":"Horwell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey, TW20 0EX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology & Immunology, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aras","family":"Kadioglu","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology & Immunology, University of Liverpool, The Ronald Ross Building, 8 West Derby St, Liverpool, L69 7BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linh","family":"Vo","sequence":"additional","affiliation":[{"name":"SporeGen Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huynh A.","family":"Hong","sequence":"additional","affiliation":[{"name":"SporeGen Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linh Hanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Huro Biotech JSC, Lot A1-8, VL3 Road, Vinh Loc 2 Industrial Park, Long Hiep Commune, Ben Luc District, Long An Province, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0575-5050","authenticated-orcid":false,"given":"Simon M.","family":"Cutting","sequence":"additional","affiliation":[{"name":"SporeGen Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"doi-asserted-by":"publisher","key":"R1","DOI":"10.1016\/j.vaccine.2012.03.016"},{"doi-asserted-by":"publisher","key":"R2","DOI":"10.1111\/j.1574-695X.2008.00415.x"},{"doi-asserted-by":"publisher","key":"R3","DOI":"10.1038\/s41598-022-16136-z"},{"doi-asserted-by":"publisher","key":"R4","DOI":"10.3389\/fmicb.2019.00447"},{"doi-asserted-by":"publisher","key":"R5","DOI":"10.3390\/vaccines10091559"},{"volume-title":"Modern Microbiological Methods","year":"1990","author":"Harwood","key":"R6"},{"doi-asserted-by":"publisher","key":"R7","DOI":"10.3920\/BM2012.0002"},{"key":"R8","first-page":"2740","article-title":"Guidance on the assessment of bacterial susceptibility to antimicrobials of human and veterinary importance","volume":"10","year":"2012","journal-title":"EFSA Journal"},{"doi-asserted-by":"publisher","key":"R9","DOI":"10.1111\/j.1365-2672.2008.03773.x"},{"doi-asserted-by":"publisher","key":"R10","DOI":"10.1177\/1091581817741840"},{"key":"R11","first-page":"65717","article-title":"International conference on Harmonisation; 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