BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial
Melanie A. Gasper, Anneke C. Hesseling, Isaac Mohar, Landon Myer, Tali Azenkot, Jo-Ann S. Passmore, Willem Hanekom, Mark F. Cotton, I. Nicholas Crispe, Donald L. Sodora, Heather B. Jaspan
Melanie A. Gasper, Anneke C. Hesseling, Isaac Mohar, Landon Myer, Tali Azenkot, Jo-Ann S. Passmore, Willem Hanekom, Mark F. Cotton, I. Nicholas Crispe, Donald L. Sodora, Heather B. Jaspan
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Clinical Research and Public Health Immunology Infectious disease

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

Abstract

BACKGROUND. 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.

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-α1 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.

TRIAL REGISTRATION. ClinicalTrials.gov NCT02062580.

FUNDING. 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.

Authors

Melanie A. Gasper, Anneke C. Hesseling, Isaac Mohar, Landon Myer, Tali Azenkot, Jo-Ann S. Passmore, Willem Hanekom, Mark F. Cotton, I. Nicholas Crispe, Donald L. Sodora, Heather B. Jaspan

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Figure 3

BCG vaccination of HIV-exposed infants is associated with an increase of activated CD4+CCR5+ HIV target cells.

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BCG vaccination of HIV-exposed infants is associated with an increase of...
(A) Longitudinal frequency of activated CD4+CCR5+HLA-DR+CD38+ T cells from birth through 14 weeks in routine (gray circles) versus delayed (black squares) BCG-vaccinated infants. Syringe graphics indicate the time of vaccination in the routine arm (gray) or the delayed arm (black). (B) Plots depicting the increase in activated CCR5+CD4+ target cells in the routine or delayed groups 6 weeks after vaccination in each group (routine: n = 37 at 0 weeks, n = 44 at 6 weeks; delayed: n = 24 at 8 weeks, n = 21 at 14 weeks; only samples with >1,000 live CD3+ cells were included in the analysis. Lines depict the medians; whiskers represent the interquartile ranges. **P < 0.01; ***P < 0.001; ****P < 0.0001.