BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial.

BACKGROUND. Bacillus Calmette-Guerin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants. METHODS. HIV-exposed infants were randomized to receive routine (at birth) or delayed (at 8 weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4(+) T cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and immune gene expression via PCR using Biomark (Fluidigm). RESULTS. Of 149 infants randomized, 92% (n = 137) were retained at 6 weeks: 71 in the routine BCG arm and 66 in the delayed arm. Routine BCG vaccination led to a 3-fold increase in systemic activation of HIV target CD4(+)CCR5(+) T cells (HLA-DR(+)CD38(+)) at 6 weeks (0.25% at birth versus 0.08% in delayed vaccination groups; P = 0.029), which persisted until 8 weeks of age when the delayed arm was vaccinated. Vaccination of the infants in the delayed arm at 8 weeks resulted in a similar increase in activated CD4(+)CCR5(+) T cells. The increase in activated T cells was associated with increased levels of MHC class II transactivator (CIITA), IL12RB1, and IFN-alpha 1 transcripts within peripheral blood mononuclear cells but minimal changes in innate cells. CONCLUSION. BCG vaccination induces immune changes in HIV-exposed infants, including an increase in the proportion of activated CCR5(+)CD4(+) HIV target cells. These findings provide insight into optimal BCG vaccine timing to minimize the risks of HIV transmissions to exposed infants while preserving potential benefits conferred by BCG vaccination.