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

Abstract

<b>BACKGROUND.</b> Bacillus Calmette-Guérin (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. <b>METHODS.</b> 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). <b>RESULTS.</b> Of 149 infants randomized, 92% (<i>n</i> = 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; <i>P</i> = 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-α1 transcripts within peripheral blood mononuclear cells but minimal changes in innate cells. <b>CONCLUSION.</b> 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. <b>TRIAL REGISTRATION.</b> ClinicalTrials.gov NCT02062580. <b>FUNDING.</b> This trial was sponsored by the Elizabeth Glaser Pediatric AIDS Foundation (MV-00-9-900-01871-0-00) and the Thrasher Foundation (NR-0095); for details, see Acknowledgments.