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
Introduction Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica 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 Salmone...
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BMJ Publishing Group
2023-11-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/13/11/e072938.full |
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| author | Melita A Gordon Ellis Owusu-Dabo Florian Marks Carsten Mantel Andrew J Pollard Brama Hanumunthadu Rachel White John A Crump Hannah Robinson Jan Jacobs Samuel Kariuki Bieke Tack Stefano Malvolti Nasir Kanji Nelly Owino Carla Ferreira Da Silva Pietro Ferruzzi Usman Nakakana Rocio Canals Maheshi Ramasamy Francis Agyapong Gianluca Breghi Fabio Fiorino Christian S. Marchello Donata Medaglini Esther M. Muthumbi Chisomo L. Msefula Tonney S. Nyirenda Robert Onsare Elena Pettini Anthony G Scott J Bassiahi Abdramane Soura Tiziana Spadafina |
| author_facet | Melita A Gordon Ellis Owusu-Dabo Florian Marks Carsten Mantel Andrew J Pollard Brama Hanumunthadu Rachel White John A Crump Hannah Robinson Jan Jacobs Samuel Kariuki Bieke Tack Stefano Malvolti Nasir Kanji Nelly Owino Carla Ferreira Da Silva Pietro Ferruzzi Usman Nakakana Rocio Canals Maheshi Ramasamy Francis Agyapong Gianluca Breghi Fabio Fiorino Christian S. Marchello Donata Medaglini Esther M. Muthumbi Chisomo L. Msefula Tonney S. Nyirenda Robert Onsare Elena Pettini Anthony G Scott J Bassiahi Abdramane Soura Tiziana Spadafina |
| collection | DOAJ |
| description | Introduction Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica 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 Salmonellae 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 S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.Method and analysis The Salmonella 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 S. Typhimurium and S. 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.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.Ethics and dissemination 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.Trial registration number EudraCT Number: 2020-000510-14. |
| first_indexed | 2024-03-09T09:07:10Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-03-09T09:07:10Z |
| publishDate | 2023-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-7f29c2eaf5e042f4a8bfa23fb84777a22023-12-02T09:50:08ZengBMJ Publishing GroupBMJ Open2044-60552023-11-01131110.1136/bmjopen-2023-072938Salmonella 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 Melita A GordonEllis Owusu-DaboFlorian MarksCarsten MantelAndrew J Pollard0Brama Hanumunthadu1Rachel White2John A CrumpHannah Robinson3Jan JacobsSamuel KariukiBieke TackStefano MalvoltiNasir Kanji4Nelly Owino5Carla Ferreira Da Silva6Pietro Ferruzzi7Usman Nakakana8Rocio Canals9Maheshi Ramasamy10Francis AgyapongGianluca BreghiFabio FiorinoChristian S. MarchelloDonata MedagliniEsther M. MuthumbiChisomo L. MsefulaTonney S. NyirendaRobert OnsareElena PettiniAnthony G Scott JBassiahi Abdramane SouraTiziana SpadafinaOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKDepartment of Paediatrics, University of Oxford, Oxford Vaccine Group, Oxford, Oxfordshire, UKDepartment of Paediatrics, University of Oxford, Oxford Vaccine Group, Oxford, Oxfordshire, UKDepartment of Paediatrics, University of Oxford, Oxford Vaccine Group, Oxford, Oxfordshire, UKDepartment of Paediatrics, University of Oxford, Oxford Vaccine Group, Oxford, Oxfordshire, UKDepartment of Paediatrics, University of Oxford, Oxford Vaccine Group, Oxford, Oxfordshire, UKDepartment of Paediatrics, University of Oxford, Oxford Vaccine Group, Oxford, Oxfordshire, UKGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyGSK Vaccines Institute for Global Health, Siena, ItalyDepartment of Paediatrics, University of Oxford, Oxford Vaccine Group, Oxford, Oxfordshire, UKIntroduction Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica 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 Salmonellae 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 S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.Method and analysis The Salmonella 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 S. Typhimurium and S. 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.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.Ethics and dissemination 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.Trial registration number EudraCT Number: 2020-000510-14.https://bmjopen.bmj.com/content/13/11/e072938.full |
| spellingShingle | Melita A Gordon Ellis Owusu-Dabo Florian Marks Carsten Mantel Andrew J Pollard Brama Hanumunthadu Rachel White John A Crump Hannah Robinson Jan Jacobs Samuel Kariuki Bieke Tack Stefano Malvolti Nasir Kanji Nelly Owino Carla Ferreira Da Silva Pietro Ferruzzi Usman Nakakana Rocio Canals Maheshi Ramasamy Francis Agyapong Gianluca Breghi Fabio Fiorino Christian S. Marchello Donata Medaglini Esther M. Muthumbi Chisomo L. Msefula Tonney S. Nyirenda Robert Onsare Elena Pettini Anthony G Scott J Bassiahi Abdramane Soura Tiziana Spadafina 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 BMJ Open |
| 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 |
| url | https://bmjopen.bmj.com/content/13/11/e072938.full |
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