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

Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia
Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia
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 2 months 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-?+) CD4 T cells. Concentrations of cytokines in supernatants were also similar in both groups.

Conclusions

Cellular immunity measured 10 weeks after BCG immunisation was similar in infants given BCG at birth and in those given BCG at 2 months 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.
4132-4139
Ritz, Nicole
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Casalaz, Dan
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Donath, Susan
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Tebruegge, Marc
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Dutta, Binita
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Connell, Tom
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Robins-Browne, Roy
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Britton, Warwick
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Hanekom, Willem
c9ec155b-a8ad-49a2-baf2-f8996b43baf9
Curtis, Nigel
60e08f70-7ce9-42b3-8074-d5df55131b12
Ritz, Nicole
ce6604a1-f373-4d76-838a-1ae75f35b20b
Casalaz, Dan
c2d6caf6-7951-4165-af38-e0a566ba613a
Donath, Susan
b1bb69fe-e708-4ec5-b98a-6bdab36e71b1
Tebruegge, Marc
2c3dff22-0b5f-48a7-bb36-ce323705f74a
Dutta, Binita
0621b33e-ae04-427c-ac38-ab40db51174a
Connell, Tom
7c1afb37-45bd-44a3-a274-20839e68f2c3
Robins-Browne, Roy
fa592da6-9054-499a-b0bc-1ce11dda8b5c
Britton, Warwick
ed6f31e6-d034-4ba7-b6de-617ca8e3d8ab
Hanekom, Willem
c9ec155b-a8ad-49a2-baf2-f8996b43baf9
Curtis, Nigel
60e08f70-7ce9-42b3-8074-d5df55131b12

Ritz, Nicole, Casalaz, Dan, Donath, Susan, Tebruegge, Marc, Dutta, Binita, Connell, Tom, Robins-Browne, Roy, Britton, Warwick, Hanekom, Willem and Curtis, Nigel (2016) Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia. Vaccine, 34 (35), 4132-4139. (doi:10.1016/j.vaccine.2016.06.077). (PMID:27396518)

Record type: Article

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 2 months 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-?+) CD4 T cells. Concentrations of cytokines in supernatants were also similar in both groups.

Conclusions

Cellular immunity measured 10 weeks after BCG immunisation was similar in infants given BCG at birth and in those given BCG at 2 months 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.

Text
Ritz_BCG_birth_delayed_manuscript_accepted version (combined).pdf - Accepted Manuscript
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More information

Accepted/In Press date: 27 June 2016
e-pub ahead of print date: 5 July 2016
Published date: 29 July 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 402103
URI: https://eprints.soton.ac.uk/id/eprint/402103
PURE UUID: d12d51a7-11a7-435f-a25b-6b2116feca08

Catalogue record

Date deposited: 01 Nov 2016 16:47
Last modified: 03 Dec 2019 06:29

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Contributors

Author: Nicole Ritz
Author: Dan Casalaz
Author: Susan Donath
Author: Marc Tebruegge
Author: Binita Dutta
Author: Tom Connell
Author: Roy Robins-Browne
Author: Warwick Britton
Author: Willem Hanekom
Author: Nigel Curtis

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