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HETEROLOGOUS IMMUNOLOGICAL EFFECTS OF EARLY BCG VACCINATION IN LOW-BIRTH-WEIGHT INFANTS

Saturday, 18th of April 2015

“BCG may accelerate the development of the neonatal immune system, mediating comprehensive protection against infections and mortality.”

HETEROLOGOUS IMMUNOLOGICAL EFFECTS OF EARLY BCG VACCINATION IN LOW-BIRTH-WEIGHT INFANTS IN GUINEA-BISSAU: A RANDOMIZED-CONTROLLED TRIAL

1. Kristoffer Jarlov Jensen1,2,3,
2. Nanna Larsen4,
3. Sofie Biering-Sørensen1,
4. Andreas Andersen1,
5. Helle Brander Eriksen1,a,
6. Ivan Monteiro3,
7. David Hougaard4,
8. Peter Aaby3,
9. Mihai G. Netea5,
10. Katie L. Flanagan6 and
11. Christine Stabell Benn1,3,7

+ Author Affiliations

1.      ¹Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen,

2.      ²Department of Cardiovascular and Renal Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

3.      ³Projécto de Saúde Bandim, Indepth Network, codex 1004, Bissau, Guinea-Bissau

4.      ⁴Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark

5.      ⁵Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

6.      ⁶Department of Immunology, Monash University, Melbourne, Australia

7.      ⁷OPEN, University of Southern Denmark/Odense University Hospital

1. Correspondence: Kristoffer Jarlov Jensen, MD, Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark (kjj@ssi.dk).

1. Previous presentation of data: Part of the present data has been presented in a preliminary form in an oral session at the 15th International Congress of Immunology, Milan, Italy, August 2014.
2. ↵a Present affiliation: Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, Denmark.

The Journal of Infectious Diseases,Volume 211, Issue 6, pp. 956-967.

Abstract below; full text is at http://jid.oxfordjournals.org/content/211/6/956.full

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.

 

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

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BCG Modulates Neonatal Innate Immune Cytokine Production J Infect Dis. (2015) 211 (6): 859-860 first published online September 9, 2014 doi:10.1093/infdis/jiu509

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1. J Infect Dis. (2015) 211 (6): 956-967. doi: 10.1093/infdis/jiu508 First published online: September 9, 2014