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. 2021 Feb 16;11(2):e040430.
doi: 10.1136/bmjopen-2020-040430.

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

Ludoviko Zirimenya #  1 , Gyaviira Nkurunungi #  2 , Jacent Nassuuna #  1 , Agnes Natukunda #  1 , Alex Mutebe  1 , Gloria Oduru  1 , Grace Kabami  1 , Hellen Akurut  1 , Caroline Onen  1 , Milly Namutebi  1 , Joel Serubanja  1 , Esther Nakazibwe  1 , Florence Akello  1 , Josephine Tumusiime  1 , Moses Sewankambo  1 , Samuel Kiwanuka  1 , Fred Kiwudhu  1 , Robert Kizindo  1 , Moses Kizza  1 , Anne Wajja  1 , Stephen Cose  1   3 , Moses Muwanga  4 , Emily Webb  5 , Alison M Elliott  1   3 ; POPVAC trial team
Collaborators, Affiliations

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

Ludoviko Zirimenya et al. BMJ Open. .

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.

Keywords: BCG; immunisation; uganda; vaccine.

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Conflict of interest statement

Competing interests: AME reports a grant from the Medical Research Council, UK (POPVAC programme funding).

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References

    1. Benn CS, Netea MG, Selin LK, et al. . A small jab - a big effect: nonspecific immunomodulation by vaccines. Trends Immunol 2013;34:431–9. 10.1016/j.it.2013.04.004 - DOI - PubMed
    1. Rieckmann A, Villumsen M, Sørup S, et al. . Vaccinations against smallpox and tuberculosis are associated with better long-term survival: a Danish case-cohort study 1971-2010. Int J Epidemiol 2017;46:695–705. 10.1093/ije/dyw120 - DOI - PMC - PubMed
    1. Prentice S, Webb EL, Dockrell HM, et al. . Investigating the non-specific effects of BCG vaccination on the innate immune system in Ugandan neonates: study protocol for a randomised controlled trial. Trials 2015;16:149. 10.1186/s13063-015-0682-5 - DOI - PMC - PubMed
    1. Biering-Sørensen S, Aaby P, Lund N, et al. . Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A Randomized Controlled Trial. Clin Infect Dis 2017;65:1183–90. 10.1093/cid/cix525 - DOI - PMC - PubMed
    1. Blok BA, Arts RJW, van Crevel R, et al. . Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines. J Leukoc Biol 2015;98:347–56. 10.1189/jlb.5RI0315-096R - DOI - PubMed

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