Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme
Introduction Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tr...
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2021
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oai:doaj.org-article:0046f191741b4bd285f9b6dcba978b902021-11-18T12:00:08ZEffect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme10.1136/bmjopen-2020-0404262044-6055https://doaj.org/article/0046f191741b4bd285f9b6dcba978b902021-02-01T00:00:00Zhttps://bmjopen.bmj.com/content/11/2/e040426.fullhttps://doaj.org/toc/2044-6055Introduction Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysis We have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and dissemination Ethics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration number ISRCTN60517191.Pontiano KaleebuEmily WebbMoses MuwangaGyaviira NkurunungiLudoviko ZirimenyaAgnes NatukundaJacent NassuunaGloria OduruCaroline NinsiimaChristopher ZziwaFlorence AkelloRobert KizindoMirriam AkelloAnne WajjaHenry LuzzeStephen CoseAlison M ElliottAlison ElliottRebecca AmonginBeatrice NassangaIrene NambuyaProssy KabuubiEmmanuel NiwagabaGrace KabamiHelen AkurutAlex MutebeMilly NamutebiCaroline OnenEsther NakazibweJosephine TumusiimeSusan AmongiMoses SewankamboDenis NsubugaSamuel KiwanukaFred KiwudhuDavid AbirigaMoses KizzaSamsi NansukusaHermelijn SmitsMaria YazdanbakhshGovert van DamPaul CorstjensSarah StaedkeJames KaweesaEdridah TukahebwaElly TumushabeProssy N KabuubiJoel SerubanjaBMJ Publishing GrouparticleMedicineRENBMJ Open, Vol 11, Iss 2 (2021) |
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Medicine R Pontiano Kaleebu Emily Webb Moses Muwanga Gyaviira Nkurunungi Ludoviko Zirimenya Agnes Natukunda Jacent Nassuuna Gloria Oduru Caroline Ninsiima Christopher Zziwa Florence Akello Robert Kizindo Mirriam Akello Anne Wajja Henry Luzze Stephen Cose Alison M Elliott Alison Elliott Rebecca Amongin Beatrice Nassanga Irene Nambuya Prossy Kabuubi Emmanuel Niwagaba Grace Kabami Helen Akurut Alex Mutebe Milly Namutebi Caroline Onen Esther Nakazibwe Josephine Tumusiime Susan Amongi Moses Sewankambo Denis Nsubuga Samuel Kiwanuka Fred Kiwudhu David Abiriga Moses Kizza Samsi Nansukusa Hermelijn Smits Maria Yazdanbakhsh Govert van Dam Paul Corstjens Sarah Staedke James Kaweesa Edridah Tukahebwa Elly Tumushabe Prossy N Kabuubi Joel Serubanja Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme |
| description |
Introduction Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysis We have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and dissemination Ethics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration number ISRCTN60517191. |
| format |
article |
| author |
Pontiano Kaleebu Emily Webb Moses Muwanga Gyaviira Nkurunungi Ludoviko Zirimenya Agnes Natukunda Jacent Nassuuna Gloria Oduru Caroline Ninsiima Christopher Zziwa Florence Akello Robert Kizindo Mirriam Akello Anne Wajja Henry Luzze Stephen Cose Alison M Elliott Alison Elliott Rebecca Amongin Beatrice Nassanga Irene Nambuya Prossy Kabuubi Emmanuel Niwagaba Grace Kabami Helen Akurut Alex Mutebe Milly Namutebi Caroline Onen Esther Nakazibwe Josephine Tumusiime Susan Amongi Moses Sewankambo Denis Nsubuga Samuel Kiwanuka Fred Kiwudhu David Abiriga Moses Kizza Samsi Nansukusa Hermelijn Smits Maria Yazdanbakhsh Govert van Dam Paul Corstjens Sarah Staedke James Kaweesa Edridah Tukahebwa Elly Tumushabe Prossy N Kabuubi Joel Serubanja |
| author_facet |
Pontiano Kaleebu Emily Webb Moses Muwanga Gyaviira Nkurunungi Ludoviko Zirimenya Agnes Natukunda Jacent Nassuuna Gloria Oduru Caroline Ninsiima Christopher Zziwa Florence Akello Robert Kizindo Mirriam Akello Anne Wajja Henry Luzze Stephen Cose Alison M Elliott Alison Elliott Rebecca Amongin Beatrice Nassanga Irene Nambuya Prossy Kabuubi Emmanuel Niwagaba Grace Kabami Helen Akurut Alex Mutebe Milly Namutebi Caroline Onen Esther Nakazibwe Josephine Tumusiime Susan Amongi Moses Sewankambo Denis Nsubuga Samuel Kiwanuka Fred Kiwudhu David Abiriga Moses Kizza Samsi Nansukusa Hermelijn Smits Maria Yazdanbakhsh Govert van Dam Paul Corstjens Sarah Staedke James Kaweesa Edridah Tukahebwa Elly Tumushabe Prossy N Kabuubi Joel Serubanja |
| author_sort |
Pontiano Kaleebu |
| title |
Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme |
| title_short |
Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme |
| title_full |
Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme |
| title_fullStr |
Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme |
| title_full_unstemmed |
Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme |
| title_sort |
effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural ugandan island adolescents: randomised controlled trial protocol a for the ‘population differences in vaccine responses’ (popvac) programme |
| publisher |
BMJ Publishing Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/0046f191741b4bd285f9b6dcba978b90 |
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