Longitudinal Changes in CD4+T-Cell Memory Responses Induced by BCG Vaccination of Newborns

Background. Improved vaccination strategies against tuberculosis are needed, such as approaches to boost immunity induced by the current vaccine, BCG. Design of these strategies has been hampered by a lack of knowledge of the kinetics of the human host response induced by neonatal BCG vaccination. Furthermore, the functional and phenotypic attributes of BCG-induced long-lived memory T-cell responses remain unclear. Methods. We assessed the longitudinal CD4 + T-cell response following BCG vaccination of human newborns. The kinetics, function, and phenotype of these cells were measured using flow cytometric whole-blood assays. Results. We showed that the BCG-specific CD4 + T-cell response peaked 6—10 weeks after vaccination and gradually waned over the first year of life. Highly activated T-helper 1 cells, predominantly expressing interferon γ, tumor necrosis factor α, and/or interleukin 2, were present at the peak response. Following contraction, BCG-specific CD4 + T cells expressed high levels of Bcl-2 and displayed a predominant CD45RA - CCR7 + central memory phenotype. However, cytokine and cytotoxic marker expression by these cells was more characteristic of effector memory cells. Conclusions. Our findings suggest that boosting of BCG-primed CD4 + T cells with heterologous tuberculosis vaccines may be best after 14 weeks of age, once an established memory response has developed.