Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2)
Introduction Despite widely available vaccinations, Streptococcus pneumoniae (SPN) remains a major cause of morbidity and mortality worldwide, causing community-acquired pneumonia, meningitis, otitis media, sinusitis and bacteraemia. Here, we summarise an ethically approved protocol for a double-bli...
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2022-07-01
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| author | Tao Chen Duolao Wang Konstantinos Liatsikos Stephen B Gordon Hassan Burhan Ben Morton Tinashe K Nyazika Bradford D Gessner Helen Hill Andrea Collins Josh Hamilton Kelly Davies Fred Fyles Phoebe Hazenberg Elizabeth Begier Angela Hyder-Wright Sherin Pojar Christopher Myerscough Jesus Reine Ryan E Robinson Britta Urban Elena Mitsi Carla Solorzano Angela Quinn Kaijie Pan Annaliesa S Anderson Christian Theilacker Daniela M Ferreira Kelly Convey James Court Madlen Farrar Lisa Hitchins Ashleigh Howard Lauren Kerruish Samuel Latham Annabel Murphy Elissavet Nikolaou Angelina Peterson |
| author_facet | Tao Chen Duolao Wang Konstantinos Liatsikos Stephen B Gordon Hassan Burhan Ben Morton Tinashe K Nyazika Bradford D Gessner Helen Hill Andrea Collins Josh Hamilton Kelly Davies Fred Fyles Phoebe Hazenberg Elizabeth Begier Angela Hyder-Wright Sherin Pojar Christopher Myerscough Jesus Reine Ryan E Robinson Britta Urban Elena Mitsi Carla Solorzano Angela Quinn Kaijie Pan Annaliesa S Anderson Christian Theilacker Daniela M Ferreira Kelly Convey James Court Madlen Farrar Lisa Hitchins Ashleigh Howard Lauren Kerruish Samuel Latham Annabel Murphy Elissavet Nikolaou Angelina Peterson |
| author_sort | Tao Chen |
| collection | DOAJ |
| description | Introduction Despite widely available vaccinations, Streptococcus pneumoniae (SPN) remains a major cause of morbidity and mortality worldwide, causing community-acquired pneumonia, meningitis, otitis media, sinusitis and bacteraemia. Here, we summarise an ethically approved protocol for a double-blind, randomised controlled trial investigating the effect of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) on pneumococcal nasopharyngeal colonisation acquisition, density and duration using experimental human pneumococcal challenge (EHPC).Methods and analysis Healthy adult participants aged 18–50 years will be randomised to receive PCV13, PPV23 or placebo and then undergo one or two EHPCs involving intranasal administration of SPN at 1-month post-vaccination with serotype 3 (SPN3) and 6 months with serotype 6B (SPN6B). Participants randomised to PCV13 and placebo will also be randomised to one of two clinically relevant SPN3 strains from distinct lineages within clonal complex 180, clades Ia and II, creating five study groups. Following inoculation, participants will be seen on days 2, 7, 14 and 23. During the follow-up period, we will monitor safety, colonisation status, density and duration, immune responses and antigenuria. The primary outcome of the study is comparing the rate of SPN3 acquisition between the vaccinated (PCV13 or PPV23) and unvaccinated (placebo) groups as defined by classical culture. Density and duration of colonisation, comparison of acquisition rates using molecular methods and evaluation of the above measurements for individual SPN3 clades and SPN6B form the secondary objectives. Furthermore, we will explore the immune responses associated with these vaccines, their effect on colonisation and the relationship between colonisation and urinary pneumococcal antigen detection.Ethics and dissemination The study is approved by the NHS Research and Ethics Committee (Reference: 20/NW/0097) and by the Medicines and Healthcare products Regulatory Agency (Reference: CTA 25753/0001/001–0001). Findings will be published in peer-reviewed journals.Trial registration number ISRCTN15728847, NCT04974294. |
| format | Article |
| id | doaj-art-13a7b19514ce48c68e2c73bb6ee12be9 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-13a7b19514ce48c68e2c73bb6ee12be92025-01-31T15:05:09ZengBMJ Publishing GroupBMJ Open2044-60552022-07-0112710.1136/bmjopen-2022-062109Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2)Tao Chen0Duolao Wang1Konstantinos Liatsikos2Stephen B Gordon3Hassan BurhanBen Morton4Tinashe K NyazikaBradford D Gessner5Helen HillAndrea Collins6Josh HamiltonKelly Davies7Fred FylesPhoebe Hazenberg8Elizabeth Begier9Angela Hyder-Wright10Sherin Pojar11Christopher Myerscough12Jesus Reine13Ryan E Robinson14Britta Urban15Elena Mitsi16Carla Solorzano17Angela Quinn18Kaijie Pan19Annaliesa S Anderson20Christian Theilacker21Daniela M Ferreira22Kelly ConveyJames CourtMadlen Farrar23Lisa HitchinsAshleigh Howard24Lauren KerruishSamuel LathamAnnabel MurphyElissavet NikolaouAngelina PetersonOrthopaedic Research Institute, Zhejiang University, Hangzhou, Zhejiang, People`s Republic of ChinaGlobal Health Trials Unit, Liverpool School of Tropical Medicine, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKMalawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi9 Global Biopharmaceutical Business, Pfizer Inc, Collegeville, Pennsylvania, USAClinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKGlobal Medical and Scientific Affairs, Pfizer Inc, New York City, New York, USALiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKClinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UKClinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UKClinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UKRespiratory Department, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKPfizer Vaccines, Pfizer Inc, Collegeville, Pennsylvania, USAPfizer Vaccines, Pfizer Inc, Collegeville, Pennsylvania, USAVaccines Research and Development, Pfizer Inc, Pearl River, New York, USAPfizer Vaccines, Pfizer Inc, Collegeville, Pennsylvania, USALiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKLiverpool Vaccine Group, Liverpool School of Tropical Medicine, Liverpool, UKIntroduction Despite widely available vaccinations, Streptococcus pneumoniae (SPN) remains a major cause of morbidity and mortality worldwide, causing community-acquired pneumonia, meningitis, otitis media, sinusitis and bacteraemia. Here, we summarise an ethically approved protocol for a double-blind, randomised controlled trial investigating the effect of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) on pneumococcal nasopharyngeal colonisation acquisition, density and duration using experimental human pneumococcal challenge (EHPC).Methods and analysis Healthy adult participants aged 18–50 years will be randomised to receive PCV13, PPV23 or placebo and then undergo one or two EHPCs involving intranasal administration of SPN at 1-month post-vaccination with serotype 3 (SPN3) and 6 months with serotype 6B (SPN6B). Participants randomised to PCV13 and placebo will also be randomised to one of two clinically relevant SPN3 strains from distinct lineages within clonal complex 180, clades Ia and II, creating five study groups. Following inoculation, participants will be seen on days 2, 7, 14 and 23. During the follow-up period, we will monitor safety, colonisation status, density and duration, immune responses and antigenuria. The primary outcome of the study is comparing the rate of SPN3 acquisition between the vaccinated (PCV13 or PPV23) and unvaccinated (placebo) groups as defined by classical culture. Density and duration of colonisation, comparison of acquisition rates using molecular methods and evaluation of the above measurements for individual SPN3 clades and SPN6B form the secondary objectives. Furthermore, we will explore the immune responses associated with these vaccines, their effect on colonisation and the relationship between colonisation and urinary pneumococcal antigen detection.Ethics and dissemination The study is approved by the NHS Research and Ethics Committee (Reference: 20/NW/0097) and by the Medicines and Healthcare products Regulatory Agency (Reference: CTA 25753/0001/001–0001). Findings will be published in peer-reviewed journals.Trial registration number ISRCTN15728847, NCT04974294.https://bmjopen.bmj.com/content/12/7/e062109.full |
| spellingShingle | Tao Chen Duolao Wang Konstantinos Liatsikos Stephen B Gordon Hassan Burhan Ben Morton Tinashe K Nyazika Bradford D Gessner Helen Hill Andrea Collins Josh Hamilton Kelly Davies Fred Fyles Phoebe Hazenberg Elizabeth Begier Angela Hyder-Wright Sherin Pojar Christopher Myerscough Jesus Reine Ryan E Robinson Britta Urban Elena Mitsi Carla Solorzano Angela Quinn Kaijie Pan Annaliesa S Anderson Christian Theilacker Daniela M Ferreira Kelly Convey James Court Madlen Farrar Lisa Hitchins Ashleigh Howard Lauren Kerruish Samuel Latham Annabel Murphy Elissavet Nikolaou Angelina Peterson Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2) BMJ Open |
| title | Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2) |
| title_full | Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2) |
| title_fullStr | Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2) |
| title_full_unstemmed | Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2) |
| title_short | Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2) |
| title_sort | protocol for a phase iv double blind randomised controlled trial to investigate the effect of the 13 valent pneumococcal conjugate vaccine and the 23 valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults preventing pneumo 2 |
| url | https://bmjopen.bmj.com/content/12/7/e062109.full |
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