期刊论文详细信息
BMC Infectious Diseases
Factors affecting immunogenicity of BCG in infants, a study in Malawi, The Gambia and the UK
Hazel M Dockrell8  Steven G Smith8  Amelia C Crampin7  Martin O Ota6  Sarah Burl3  Katie L Flanagan4  Joseph R Fitchett8  Anne Ben-Smith5  John Raynes8  Sian Floyd7  Hazzie Mvula5  Maeve K Lalor1  Patricia Gorak-Stolinska8  Yun-Gyoung Hur2 
[1] Current address: Public Health England, London, UK;Current address: Yonsei University College of Medicine, Seoul, South Korea;Current address: Paediatric Infectious Diseases, Imperial College London, London, UK;Current address: Monash University, Prahran, Victoria, Australia;Karonga Prevention Study, PO Box 46, Chilumba, Karonga District, Malawi;Medical Research Council Unit, PO Box 273, Fajara, The Gambia;Department of Infectious Disease Epidemiology, Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK;Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine London WC1E 7HT, UK
关键词: Zinc;    M. tuberculosis PPD;    Infant immune response;    Cytokine;    CRP;    BCG vaccination;   
Others  :  1134181
DOI  :  10.1186/1471-2334-14-184
 received in 2013-12-06, accepted in 2014-03-31,  发布年份 2014
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【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2014 Hur et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]World Health Organisation: Global tuberculosis report. 2013. [http://apps.who.int/iris/bitstream/10665/91355/1/9789241564656_eng.pdf webcite]
  • [2]Fine PE: Variation in protection by BCG: implications of and for heterologous immunity. Lancet 1995, 346:1339-1345.
  • [3]Wilson ME, Fineberg HV, Colditz GA: Geographic latitude and the efficacy of bacillus Calmette-Guerin vaccine. Clin Infect Dis 1995, 20:982-991.
  • [4]Lalor MK, Ben-Smith A, Gorak-Stolinska P, Weir RE, Floyd S, Blitz R, Mvula H, Newport MJ, Branson K, McGrath N, Crampin AC, Fine PE, Dockrell HM: Population differences in immune responses to Bacille Calmette-Guerin vaccination in infancy. J Infect Dis 2009, 199:795-800.
  • [5]Dewey KG, Brown KH: Update on technical issues concerning complementary feeding of young children in developing countries and implications for intervention programs. Food Nutr Bull 2003, 24:5-28.
  • [6]Dardenne M: Zinc and immune function. Eur J Clin Nutr 2002, 56(Suppl 3):S20-S23.
  • [7]Fischer Walker C, Black RE: Zinc and the risk for infectious disease. Annu Rev Nutr 2004, 24:255-275.
  • [8]Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A: Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr 1999, 135:689-697.
  • [9]IZiNCG: International Zinc Nutrition Consultative Group: IZiNCG Technical Brief; Assessing population zinc status with serum zinc concentration. 2012. [http://www.izincg.org/Media/Default/Publications/Files/IZiNCG_TechBrief2_2012.pdf webcite]
  • [10]Fischer Walker CL, Ezzati M, Black RE: Global and regional child mortality and burden of disease attributable to zinc deficiency. Eur J Clin Nutr 2009, 63:591-597.
  • [11]Sandstrom B, Sandberg AS: Inhibitory effects of isolated inositol phosphates on zinc absorption in humans. J Trace Elements Electrolytes Health Dis 1992, 6:99-103.
  • [12]Clyne B, Olshaker JS: The C-reactive protein. J Emerg Med 1999, 17:1019-1025.
  • [13]Pulliam PN, Attia MW, Cronan KM: C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics 2001, 108:1275-1279.
  • [14]Black GF, Weir RE, Floyd S, Bliss L, Warndorff DK, Crampin AC, Ngwira B, Sichali L, Nazareth B, Blackwell JM, Branson K, Chaguluka SD, Donovan L, Jarman E, King E, Fine PE, Dockrell HM: BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet 2002, 359:1393-1401.
  • [15]Black GF, Dockrell HM, Crampin AC, Floyd S, Weir RE, Bliss L, Sichali L, Mwaungulu L, Kanyongoloka H, Ngwira B, Warndorff DK, Fine PE: Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi. J Infect Dis 2001, 184:322-329.
  • [16]Lalor MK: Infant immune responses following BCG vaccination in the UK and Malawi. PhD thesis. London: University of London, London School of Hygiene & Tropical Medicine; 2009.
  • [17]Fitchett JR: Infant and maternal immune responses to tuberculosis mycobacterial antigens post-BCG vaccination in the gambia. In MSc thesis. London: University of London, London School of Hygiene & Tropical Medicine; 2010.
  • [18]Lalor MK, Floyd S, Gorak-Stolinska P, Ben-Smith A, Weir RE, Smith SG, Newport MJ, Blitz R, Mvula H, Branson K, McGrath N, Crampin AC, Fine PE, Dockrell HM: BCG vaccination induces different cytokine profiles following infant BCG vaccination in the UK and Malawi. J Infect Dis 2011, 204:1075-1085.
  • [19]Pourcyrous M, Korones SB, Crouse D, Bada HS: Interleukin-6, C-reactive protein, and abnormal cardiorespiratory responses to immunization in premature infants. Pediatrics 1998, 101:E3.
  • [20]Ritz N, Curtis N: Mapping the global use of different BCG vaccine strains. Tuberculosis (Edinb) 2009, 89:248-251.
  • [21]Anderson EJ, Webb EL, Mawa PA, Kizza M, Lyadda N, Nampijja M, Elliott AM: The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda. Vaccine 2012, 30:2083-2089.
  • [22]Ritz N, Dutta B, Donath S, Casalaz D, Connell TG, Tebruegge M, Robins-Browne R, Hanekom WA, Britton WJ, Curtis N: The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial. Am J Respir Crit Care Med 2012, 185:213-222.
  • [23]Kagina BM, Abel B, Bowmaker M, Scriba TJ, Gelderbloem S, Smit E, Erasmus M, Nene N, Walzl G, Black G, Hussey GD, Hesseling AC, Hanekom WA: Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response. Vaccine 2009, 27:5488-5495.
  • [24]Marchant A, Goetghebuer T, Ota MO, Wolfe I, Ceesay SJ, De Groote D, Corrah T, Bennett S, Wheeler J, Huygen K, Aaby P, McAdam KP, Newport MJ: Newborns develop a Th1-type immune response to mycobacterium bovis bacillus Calmette-Guerin vaccination. J Immunol 1999, 163:2249-2255.
  • [25]Lutwama F, Kagina BM, Wajja A, Waiswa F, Mansoor N, Kirimunda S, Hughes EJ, Kiwanuka N, Joloba ML, Musoke P, Scriba TJ, Mayanja-Kizza H, Day CL, Hanekom WA: Distinct T-cell responses when BCG vaccination is delayed from birth to 6 weeks of age in Ugandan infants. J Infect Dis 2014, 209:887-897.
  • [26]Barrios C, Brawand P, Berney M, Brandt C, Lambert PH, Siegrist CA: Neonatal and early life immune responses to various forms of vaccine antigens qualitatively differ from adult responses: predominance of a Th2-biased pattern which persists after adult boosting. Eur J Immunol 1996, 26:1489-1496.
  • [27]Hur YG, Crampin AC, Chisambo C, Kanyika J, Houben R, Ndhlovu R, Mzembe T, Lalor MK, Saul J, Branson K, Stanley C, Ngwira B, French N, Ottenhoff TH, Dockrell HM, Gorak-Stolinska P: Identification of immunological biomarkers which may differentiate latent tuberculosis from exposure to environmental nontuberculous mycobacteria in children. Clin Vaccine Immunol 2014, 21:133-142.
  • [28]Walzl G, Ronacher K, Hanekom W, Scriba TJ, Zumla A: Immunological biomarkers of tuberculosis. Nat Rev Immunol 2011, 11:343-354.
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