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 4

Fluidigm immune gene expression analysis in routine and delayed BCG-vaccinated HIV-exposed infants at 2 weeks of age.

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Fluidigm immune gene expression analysis in routine and delayed BCG-vacc...
Expression of 48 genes (including 2 housekeeping genes) was measured via Biomark (Fluidigm) quantitative real-time PCR analysis at 2 weeks of age when only the “routine” arm had received vaccination. (A) Fold change of gene expression between the routine versus delayed BCG-vaccinated groups. (B) –ΔCt (calculated by Ctgene of interest – CtGAPDH) of genes that demonstrated significantly differential expression between the groups. Lines depict the median; whiskers depict interquartile range. (C) Linear regression of gene expression of CIITA, CD8A, IL12RB1, IFNA1, and IL1A as determined at 2 weeks of age (–dCt expression value is shown on the x axis) and subsequent activation of activated CD4+CCR5+HLA-DR+CD38+ HIV target cells at 6 weeks in all infants combined (shown on the y axis).