The University of Southampton
University of Southampton Institutional Repository

The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial

The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial
The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial
Rationale: Approximately 100 million doses of bacille Calmette-Guérin (BCG) vaccine are given each year to protect against tuberculosis (TB). More than 20 genetically distinct BCG vaccine strains are in use worldwide. Previous studies suggest that BCG vaccine strain influences the immune response and protection against TB. Current data on which BCG vaccine strain induces the optimal immune response in humans are insufficient.

Objectives: To compare the immune response to three different BCG vaccine strains given to infants at birth.

Methods: Newborn infants in a tertiary women's hospital were immunized at birth with one of three BCG vaccine strains. A stratified randomization according to the mother's region of birth was used.

Measurements and main results: The presence of mycobacterial-specific polyfunctional CD4 T cells measured by flow cytometry 10 weeks after immunization. Of the 209 infants immunized, data from 164 infants were included in the final analysis (BCG-Denmark, n = 54; BCG-Japan, n = 54; BCG-Russia, n = 57). The proportion of polyfunctional CD4 T cells was significantly higher in infants immunized with BCG-Denmark (0.013%) or BCG-Japan (0.016%) than with BCG-Russia (0.007%) (P = 0.018 and P = 0.003, respectively). Infants immunized with BCG-Japan had higher concentrations of secreted Th1 cytokines; infants immunized with BCG-Denmark had higher proportions of CD107-expressing cytotoxic CD4 T cells.

Conclusions: There are significant differences in the immune response induced by different BCG vaccine strains in newborn infants. Immunization with BCG-Denmark or BCG-Japan induced higher frequencies of mycobacterial-specific polyfunctional and cytotoxic T cells and higher concentrations of Th1 cytokines. These findings have potentially important implications for global antituberculosis immunization policies and future tuberculosis vaccine trials.
tuberculosis, BCG, immune response, protection, vaccine strain
1073-449X
213-222
Ritz, Nicole
ce6604a1-f373-4d76-838a-1ae75f35b20b
Dutta, Binita
0621b33e-ae04-427c-ac38-ab40db51174a
Donath, Susan
b1bb69fe-e708-4ec5-b98a-6bdab36e71b1
Casalaz, Dan
c2d6caf6-7951-4165-af38-e0a566ba613a
Connell, Tom G.
7330eed5-809b-4e01-9ac8-8dd2aef795c3
Tebruegge, Marc
2c3dff22-0b5f-48a7-bb36-ce323705f74a
Robins-Browne, Roy
fa592da6-9054-499a-b0bc-1ce11dda8b5c
Hanekom, Willem A.
fa74e1f8-0353-45a7-93d4-81ba5ca55341
Britton, Warwick J.
e9dce67a-c05f-4ac3-bb13-3334a646868a
Curtis, Nigel
60e08f70-7ce9-42b3-8074-d5df55131b12
Ritz, Nicole
ce6604a1-f373-4d76-838a-1ae75f35b20b
Dutta, Binita
0621b33e-ae04-427c-ac38-ab40db51174a
Donath, Susan
b1bb69fe-e708-4ec5-b98a-6bdab36e71b1
Casalaz, Dan
c2d6caf6-7951-4165-af38-e0a566ba613a
Connell, Tom G.
7330eed5-809b-4e01-9ac8-8dd2aef795c3
Tebruegge, Marc
2c3dff22-0b5f-48a7-bb36-ce323705f74a
Robins-Browne, Roy
fa592da6-9054-499a-b0bc-1ce11dda8b5c
Hanekom, Willem A.
fa74e1f8-0353-45a7-93d4-81ba5ca55341
Britton, Warwick J.
e9dce67a-c05f-4ac3-bb13-3334a646868a
Curtis, Nigel
60e08f70-7ce9-42b3-8074-d5df55131b12

Ritz, Nicole, Dutta, Binita, Donath, Susan, Casalaz, Dan, Connell, Tom G., Tebruegge, Marc, Robins-Browne, Roy, Hanekom, Willem A., Britton, Warwick J. and Curtis, Nigel (2012) The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial. American Journal of Respiratory and Critical Care Medicine, 185 (2), 213-222. (doi:10.1164/rccm.201104-0714OC). (PMID:22071384)

Record type: Article

Abstract

Rationale: Approximately 100 million doses of bacille Calmette-Guérin (BCG) vaccine are given each year to protect against tuberculosis (TB). More than 20 genetically distinct BCG vaccine strains are in use worldwide. Previous studies suggest that BCG vaccine strain influences the immune response and protection against TB. Current data on which BCG vaccine strain induces the optimal immune response in humans are insufficient.

Objectives: To compare the immune response to three different BCG vaccine strains given to infants at birth.

Methods: Newborn infants in a tertiary women's hospital were immunized at birth with one of three BCG vaccine strains. A stratified randomization according to the mother's region of birth was used.

Measurements and main results: The presence of mycobacterial-specific polyfunctional CD4 T cells measured by flow cytometry 10 weeks after immunization. Of the 209 infants immunized, data from 164 infants were included in the final analysis (BCG-Denmark, n = 54; BCG-Japan, n = 54; BCG-Russia, n = 57). The proportion of polyfunctional CD4 T cells was significantly higher in infants immunized with BCG-Denmark (0.013%) or BCG-Japan (0.016%) than with BCG-Russia (0.007%) (P = 0.018 and P = 0.003, respectively). Infants immunized with BCG-Japan had higher concentrations of secreted Th1 cytokines; infants immunized with BCG-Denmark had higher proportions of CD107-expressing cytotoxic CD4 T cells.

Conclusions: There are significant differences in the immune response induced by different BCG vaccine strains in newborn infants. Immunization with BCG-Denmark or BCG-Japan induced higher frequencies of mycobacterial-specific polyfunctional and cytotoxic T cells and higher concentrations of Th1 cytokines. These findings have potentially important implications for global antituberculosis immunization policies and future tuberculosis vaccine trials.

This record has no associated files available for download.

More information

e-pub ahead of print date: 3 November 2011
Published date: 15 January 2012
Keywords: tuberculosis, BCG, immune response, protection, vaccine strain
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 337537
URI: http://eprints.soton.ac.uk/id/eprint/337537
ISSN: 1073-449X
PURE UUID: 397c58b7-1375-44ec-9804-1cdc4a643d03

Catalogue record

Date deposited: 26 Apr 2012 15:54
Last modified: 14 Mar 2024 10:54

Export record

Altmetrics

Contributors

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×