Population differences in vaccine responses (POPVAC): scientific rationale and cross-cutting analyses for three linked, randomised controlled trials assessing the role, reversibility and mediators of immunomodulation by chronic infections in the tropics. Issue 2 (16th February 2021)

• Record Type: Journal Article
• Authors: Nkurunungi, Gyaviira; Zirimenya, Ludoviko; Natukunda, Agnes; Nassuuna, Jacent; Oduru, Gloria; Ninsiima, Caroline; Zziwa, Christopher; Akello, Florence; Kizindo, Robert; Akello, Mirriam; Kaleebu, Pontiano; Wajja, Anne; Luzze, Henry; Cose, Stephen; Webb, Emily; Elliott, Alison M
• Other Names: author non-byline.; Elliott Alison author non-byline.; Zirimenya Ludoviko author non-byline.; Nkurunungi Gyaviira author non-byline.; Cose Stephen author non-byline.; Amongin Rebecca author non-byline.; Nassanga Beatrice author non-byline.; Nassuuna Jacent author non-byline.; Nambuya Irene author non-byline.; Kabuubi Prossy author non-byline.; Niwagaba Emmanuel author non-byline.; Oduru Gloria author non-byline.; Kabami Grace author non-byline.; Webb Emily author non-byline.; Natukunda Agnes author non-byline.; Akurut Helen author non-byline.; Mutebe Alex author non-byline.; Wajja Anne author non-byline.; Namutebi Milly author non-byline.; Zziwa Christopher author non-byline.; Onen Caroline author non-byline.; Nakazibwe Esther author non-byline.; Tumusiime Josephine author non-byline.; Ninsiima Caroline author non-byline.; Amongi Susan author non-byline.; Akello Florence author non-byline.; Akello Mirriam author non-byline.; Kizindo Robert author non-byline.; Sewankambo Moses author non-byline.; Nsubuga Denis author non-byline.; Kiwanuka Samuel author non-byline.; Kiwudhu Fred author non-byline.; Abiriga David author non-byline.; Kizza Moses author non-byline.; Nansukusa Samsi author non-byline.; Kaleebu Pontiano author non-byline.; Smits Hermelijn author non-byline.; Yazdanbakhsh Maria author non-byline.; Dam Govert van author non-byline.; Corstjens Paul author non-byline.; Staedke Sarah author non-byline.; Luzze Henry author non-byline.; Kaweesa James author non-byline.; Tukahebwa Edridah author non-byline.; Tumushabe Elly author non-byline.; Muwanga Moses author non-byline.;
• Is Part Of: BMJ open. Volume 11:Issue 2(2021)
• Publication Date: 2021-02-16
• Subjects: infection control -- parasitology -- public health -- immunology -- epidemiology -- paediatric infectious disease & immunisation; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2020-040425
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: Vaccine-specific immune responses vary between populations and are often impaired in low income, rural settings. Drivers of these differences are not fully elucidated, hampering identification of strategies for optimising vaccine effectiveness. We hypothesise that urban–rural (and regional and international) differences in vaccine responses are mediated to an important extent by differential exposure to chronic infections, particularly parasitic infections. Methods and analysis: Three related trials sharing core elements of study design and procedures (allowing comparison of outcomes across the trials) will test the effects of (1) individually randomised intervention against schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus Calmette-Guérin (BCG) revaccination (trial C), on a common set of vaccine responses. We will enrol adolescents from Ugandan schools in rural high-schistosomiasis (trial A) and rural high-malaria (trial B) settings and from an established urban birth cohort (trial C). All participants will receive BCG on day '0'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. Primary outcomes are BCG-specific IFN-γ responses (8 weeks after BCG) and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine effects of interventions on correlates of protective immunity, vaccine response waning, priming versus boosting immunisations, and parasite infection status and intensity. Overarching analyses will compare outcomes between the three trial settings. Sample archives will offer opportunities for exploratory evaluation of the role of immunological and 'trans-kingdom' mediators in parasite modulation of vaccine-specific responses. 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 numbers: ISRCTN60517191, ISRCTN62041885, ISRCTN10482904 .