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J Infect Dis. 2015 Mar 15;211(6):956-67. doi: 10.1093/infdis/jiu508. Epub 2014 Sep 9.

Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: a randomized-controlled trial.

Author information

1
Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Department of Cardiovascular and Renal Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark Projécto de Saúde Bandim, Indepth Network, codex 1004, Bissau, Guinea-Bissau.
2
Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
3
Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen.
4
Projécto de Saúde Bandim, Indepth Network, codex 1004, Bissau, Guinea-Bissau.
5
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
6
Department of Immunology, Monash University, Melbourne, Australia.
7
Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Projécto de Saúde Bandim, Indepth Network, codex 1004, Bissau, Guinea-Bissau OPEN, University of Southern Denmark/Odense University Hospital.

Abstract

BACKGROUND:

Bacillus Calmette-Guérin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia.

METHODS:

Within a randomized trial in LBW infants in Guinea-Bissau of early BCG vs the usual postponed BCG, a subgroup was bled 4 weeks after randomization. Levels of interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured from whole-blood assays stimulated with innate agonists to Toll-like receptor (TLR)-2, -4 or -7/8, or purified protein derivative (PPD).

RESULTS:

Among 467 infants, BCG significantly increased the in vitro cytokine responses to purified protein derivative of Mycobacterium tuberculosis (PPD), as expected. BCG was also associated with increased responses to heterologous innate stimulation, particularly of the cytokines IL-1β, IL-6, TNF-α, and IFN-γ.

CONCLUSION:

Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro-inflammatory cytokines. BCG may accelerate the development of the neonatal immune system, mediating comprehensive protection against infections and mortality.

KEYWORDS:

Africa; BCG; cytokines; heterologous immunity; infants; nonspecific effects

PMID:
25210141
PMCID:
PMC4340366
DOI:
10.1093/infdis/jiu508
[Indexed for MEDLINE]
Free PMC Article

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