BMJ Open (Feb 2021)
Impact of BCG revaccination on the response to unrelated vaccines in a Ugandan adolescent birth cohort: randomised controlled trial protocol C for the ‘POPulation differences in VACcine responses’ (POPVAC) programme
- 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,
- Rebecca Amongin,
- Beatrice Nassanga,
- Irene Nambuya,
- Prossy Kabuubi,
- Emmanuel Niwagaba,
- Grace Kabami,
- 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,
- Joel Serubanja,
- Hellen Akurut
Affiliations
- Gyaviira Nkurunungi
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Ludoviko Zirimenya
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Agnes Natukunda
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Jacent Nassuuna
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Gloria Oduru
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Caroline Ninsiima
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Christopher Zziwa
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Florence Akello
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Robert Kizindo
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Mirriam Akello
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Anne Wajja
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Henry Luzze
- Uganda National Expanded Program on Immunisation, Ministry of Health, Kampala, Uganda
- Stephen Cose
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Alison M Elliott
- Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda
- Rebecca Amongin
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Beatrice Nassanga
- Irene Nambuya
- Prossy Kabuubi
- Emmanuel Niwagaba
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Grace Kabami
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Alex Mutebe
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Milly Namutebi
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Caroline Onen
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Esther Nakazibwe
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Wakiso, Uganda
- Josephine Tumusiime
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Wakiso, Uganda
- Susan Amongi
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Moses Sewankambo
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Denis Nsubuga
- Samuel Kiwanuka
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Fred Kiwudhu
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Wakiso, Uganda
- David Abiriga
- Moses Kizza
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Wakiso, Uganda
- Samsi Nansukusa
- Hermelijn Smits
- Maria Yazdanbakhsh
- 6Leiden University Medical Center, The Netherlands
- Govert van Dam
- Paul Corstjens
- 1Leiden University Medical Center, The Netherlands
- Sarah Staedke
- 7Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK
- James Kaweesa
- Vector Control Division, Republic of Uganda Ministry of Health, Kampala, Uganda
- Edridah Tukahebwa
- Elly Tumushabe
- Joel Serubanja
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Wakiso, Uganda
- Hellen Akurut
- Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Wakiso, Uganda
- DOI
- https://doi.org/10.1136/bmjopen-2020-040430
- Journal volume & issue
-
Vol. 11,
no. 2
Abstract
Introduction There is evidence that BCG immunisation may protect against unrelated infectious illnesses. This has led to the postulation that administering BCG before unrelated vaccines may enhance responses to these vaccines. This might also model effects of BCG on unrelated infections.Methods and analysis To test this hypothesis, we have designed a randomised controlled trial of BCG versus no BCG immunisation to determine the effect of BCG on subsequent unrelated vaccines, among 300 adolescents (aged 13–17 years) from a Ugandan birth cohort. Our schedule will comprise three main immunisation days (week 0, week 4 and week 28): BCG (or no BCG) revaccination at week 0; yellow fever (YF-17D), oral typhoid (Ty21a) and human papillomavirus (HPV) prime at week 4; and HPV boost and tetanus/diphtheria (Td) boost at week 28. Primary outcomes are anti-YF-17D neutralising antibody titres, Salmonella typhi lipopolysaccharide-specific IgG concentration, IgG specific for L1-proteins of HPV-16/HPV-18 and tetanus and diphtheria toxoid-specific IgG concentration, all assessed at 4 weeks after immunisation with YF, Ty21a, HPV and Td, respectively. Secondary analyses will determine effects on correlates of protective immunity (where recognised correlates exist), on vaccine response waning and on whether there are differential effects on priming versus boosting immunisations. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of BCG revaccination on vaccine responses. Further analyses will assess which life course exposures influence vaccine responses in adolescence.Ethics and dissemination Ethics approval has been obtained from relevant Ugandan and UK ethics committees. 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 ISRCTN10482904.