Salmonella 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
<p><strong>Introduction</strong> Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by <i>Salmonella enterica</i> serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023
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| _version_ | 1797111763077955584 |
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| author | Hanumunthadu, B Kanji, N Owino, N Ferreira Da Silva, C Robinson, H White, R Ferruzzi, P Nakakana, U Canals, R Pollard, AJ Ramasamy, M |
| author2 | Vacc-iNTS Consortium |
| author_facet | Vacc-iNTS Consortium Hanumunthadu, B Kanji, N Owino, N Ferreira Da Silva, C Robinson, H White, R Ferruzzi, P Nakakana, U Canals, R Pollard, AJ Ramasamy, M |
| author_sort | Hanumunthadu, B |
| collection | OXFORD |
| description | <p><strong>Introduction</strong> Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by <i>Salmonella enterica</i> serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal <i>Salmonellae</i> 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 <i>S.</i> Typhimurium and <i>S.</i> Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.</p>
<p><strong>Method and analysis</strong> The <i>Salmonella</i> 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 <i>S.</i> Typhimurium and <i>S.</i> 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.<br>
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.<br>
<p><strong>Ethics and dissemination</strong> Ethical approval for this study has been obtained from the South Central—Oxford 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.</p>
<p><strong>Trial registration number</strong> EudraCT Number: 2020-000510-14.</p> |
| first_indexed | 2024-03-07T08:14:57Z |
| format | Journal article |
| id | oxford-uuid:fa05855b-3b83-47ca-a14b-2b676dd731ab |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:14:57Z |
| publishDate | 2023 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:fa05855b-3b83-47ca-a14b-2b676dd731ab2023-12-13T13:18:23ZSalmonella Vaccine Study in Oxford (SALVO) trial: protocol for an observer-participant blind randomised placebo-controlled trial of the iNTS-GMMA vaccine within a European cohortJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fa05855b-3b83-47ca-a14b-2b676dd731abEnglishSymplectic ElementsBMJ Publishing Group2023Hanumunthadu, BKanji, NOwino, NFerreira Da Silva, CRobinson, HWhite, RFerruzzi, PNakakana, UCanals, RPollard, AJRamasamy, MVacc-iNTS Consortium<p><strong>Introduction</strong> Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by <i>Salmonella enterica</i> serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal <i>Salmonellae</i> 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 <i>S.</i> Typhimurium and <i>S.</i> Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.</p> <p><strong>Method and analysis</strong> The <i>Salmonella</i> 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 <i>S.</i> Typhimurium and <i>S.</i> 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.<br> 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.<br> <p><strong>Ethics and dissemination</strong> Ethical approval for this study has been obtained from the South Central—Oxford 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.</p> <p><strong>Trial registration number</strong> EudraCT Number: 2020-000510-14.</p> |
| spellingShingle | Hanumunthadu, B Kanji, N Owino, N Ferreira Da Silva, C Robinson, H White, R Ferruzzi, P Nakakana, U Canals, R Pollard, AJ Ramasamy, M Salmonella 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 |
| title | Salmonella 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 |
| title_full | Salmonella 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 |
| title_fullStr | Salmonella 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 |
| title_full_unstemmed | Salmonella 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 |
| title_short | Salmonella 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 |
| title_sort | salmonella 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 |
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