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Factors affecting immunogenicity of BCG in infants, a study in Malawi, The Gambia and the UK

Yun-Gyoung Hur156*, Patricia Gorak-Stolinska1, Maeve K Lalor17, Hazzie Mvula2, Sian Floyd3, John Raynes1, Anne Ben-Smith12, Joseph R Fitchett1, Katie L Flanagan48, Sarah Burl49, Martin O Ota4, Amelia C Crampin23, Steven G Smith1 and Hazel M Dockrell1

Author Affiliations

1 Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine London WC1E 7HT, UK

2 Karonga Prevention Study, PO Box 46, Chilumba, Karonga District, Malawi

3 Department of Infectious Disease Epidemiology, Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK

4 Medical Research Council Unit, PO Box 273, Fajara, The Gambia

5 Department of Microbiology and Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, 134, Sinchondong, Seodaemun-gu, Seoul 120-752, South Korea

6 Current address: Yonsei University College of Medicine, Seoul, South Korea

7 Current address: Public Health England, London, UK

8 Current address: Monash University, Prahran, Victoria, Australia

9 Current address: Paediatric Infectious Diseases, Imperial College London, London, UK

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BMC Infectious Diseases 2014, 14:184  doi:10.1186/1471-2334-14-184

Published: 5 April 2014



BCG immunogenicity in infants differs between populations and these differences have been attributed to various factors. In this study, the influence of geographical location, season of birth, timing of vaccination, micronutrient status (zinc) and inflammatory status (C-reactive protein, CRP) were assessed.


Immunogenicity was assessed by cytokine signature in culture supernatants from diluted whole blood samples stimulated with M. tuberculosis PPD, using a multiplex bead assay. Results were correlated with the plasma zinc and CRP concentrations at the time of sampling, and with interview and household data. BCG vaccinated infants were recruited in Malawi, The Gambia and the UK.


In Malawi, infants vaccinated within the first week after birth showed lower production of most cytokines measured than those vaccinated later. The number of cytokines showing significant differences between Malawian and Gambian infants decreased after adjusting for season of birth. In Malawi, a proportion of infants had zinc deficiency and elevated plasma CRP (>10 mg/L), but neither zinc deficiency nor high CRP was associated with production of any of the cytokines measured.


The cytokine/chemokine signatures observed in response to M. tuberculosis PPD in infants at 3 months post BCG vaccination were affected by geographical location, season of birth, and timing of vaccination but not associated with the concentration of plasma zinc or inflammatory status. These factors should be considered in future trials of new TB vaccines.

BCG vaccination; CRP; Cytokine; Infant immune response; M. tuberculosis PPD; Zinc