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

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)

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.

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