Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia

Nicole Ritz; Dan Casalaz; Susan Donath; Marc Tebruegge; Binita Dutta; Tom G Connell; Roy Robins-Browne; Warwick J Britton; Willem A Hanekom; Nigel Curtis

doi:10.1016/j.vaccine.2016.06.077

Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia

Vaccine. 2016 Jul 29;34(35):4132-4139. doi: 10.1016/j.vaccine.2016.06.077. Epub 2016 Jul 5.

Authors

Affiliations

¹ Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia; University of Basel Children's Hospital Basel, Infectious Diseases Unit and Paediatric Pharmacology, Basel, Switzerland. Electronic address: nicole.ritz@unibas.ch.
² Department of Paediatrics, The Mercy Hospital for Women, Heidelberg, Australia.
³ Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, Australia.
⁴ Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia; Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, and Institute for Life Sciences, University of Southampton, Southampton, UK.
⁵ Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia.
⁶ Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia.
⁷ Department of Paediatrics, The University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Australia.
⁸ Centenary Institute of Cancer Medicine and Cell Biology and Department of Medicine, University of Sydney, Camperdown, Australia.
⁹ South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.

PMID: 27396518
DOI: 10.1016/j.vaccine.2016.06.077

Abstract

Background: More than 120 million doses of BCG vaccine are administered worldwide each year. Most infants are given BCG at birth in accordance with WHO recommendations. However, the effect of the maturing neonatal immune system on the immune response and protection conferred by BCG remains uncertain. Previous studies investigating the influence of age at immunisation on the immune response induced by BCG have reported conflicting results. This study compared BCG given at birth and at two months of age in infants in Australia.

Methods: Infants born in Melbourne were randomly allocated to immunisation with BCG-Denmark at birth or two months of age. Ten weeks after immunisation, anti-mycobacterial immune responses were measured in a whole blood assay using intracellular cytokine assays and xMAP multiplex cytokine analysis.

Results: Result from 98 BCG-immunised infants were included in the final analysis. BCG immunisation at birth (n=54) and at 2months of age (n=44) induced comparable proportions of mycobacteria-specific cytokine-producing CD4 and CD8 T cells, as well as comparable proportions of polyfunctional (TNF(+) IL-2(+) IFN-γ(+)) CD4 T cells. Concentrations of cytokines in supernatants were also similar in both groups.

Conclusions: Cellular immunity measured 10weeks after BCG immunisation was similar in infants given BCG at birth and in those given BCG at 2months of age. Although definitive correlates of protection against TB remain uncertain, these results suggest that delaying BCG immunisation does not confer any immunological advantage in cellular immunity.

Keywords: Bacille Calmette-Guérin; HIV; Immune maturation; TB; Tuberculosis; Vaccine.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Australia
BCG Vaccine / administration & dosage*
BCG Vaccine / therapeutic use
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology*
Cytokines / immunology*
Female
Humans
Immunity, Cellular*
Infant
Infant, Newborn
Male
Tuberculosis / prevention & control

Substances

BCG Vaccine
Cytokines