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Invasive non-typhoidal<jats:italic>Salmonellae<\/jats:italic>serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing<jats:italic>S<\/jats:italic>. Typhimurium and<jats:italic>S<\/jats:italic>. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method and analysis<\/jats:title><jats:p>The<jats:italic>Salmonella<\/jats:italic>Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of<jats:italic>S<\/jats:italic>. Typhimurium and<jats:italic>S<\/jats:italic>. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.<\/jats:p><jats:p>The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>Ethical approval for this study has been obtained from the South Central\u2014Oxford A Research Ethics Committee (Ethics REF:22\/SC\/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p>EudraCT Number: 2020-000510-14.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2023-072938","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T17:10:16Z","timestamp":1699981816000},"page":"e072938","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["<i>Salmonella<\/i>Vaccine Study in Oxford (SALVO) trial: protocol for an observer-participant blind randomised placebo-controlled trial of the iNTS-GMMA vaccine within a European cohort"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6263-2327","authenticated-orcid":false,"given":"Brama","family":"Hanumunthadu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasir","family":"Kanji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Owino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Ferreira Da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Ferruzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usman","family":"Nakakana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Canals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-719X","authenticated-orcid":false,"given":"Andrew J","family":"Pollard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maheshi","family":"Ramasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"2023111409101008000_13.11.e072938.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30418-9"},{"key":"2023111409101008000_13.11.e072938.2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2106.140999"},{"key":"2023111409101008000_13.11.e072938.3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(11)61752-2"},{"key":"2023111409101008000_13.11.e072938.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2021.06.029"},{"key":"2023111409101008000_13.11.e072938.5","doi-asserted-by":"crossref","unstructured":"Feasey NA , Everett D , Faragher EB , et al . 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