BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial
BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial
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DOI：
10.1172/jci.insight.91963
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发表时间：
2017-04-06
期刊：
影响因子：
8
通讯作者：
Jaspan, Heather B.
中科院分区：
文献类型：
--
作者：
Gasper, Melanie A.;Hesseling, Anneke C.;Jaspan, Heather B.
背景卡介苗（BCG）在出生时接种，以保护非洲各地的婴儿免受结核病的侵害，大多数围产期HIV-1传播发生在非洲。我们研究了卡介苗接种是否改变了南非HIV暴露婴儿中活化的HIV靶T细胞的水平。暴露于HIV的婴儿被随机分配接受常规（出生时）或延迟（8周）BCG疫苗接种。使用Biomark（Fluidigm），通过流式细胞术和PCR免疫基因表达评估活化和表达CCR 5的外周血CD 4（+）T细胞、单核细胞和NK细胞频率。在149名随机分组的婴儿中，92%（n = 137）在6周时保留了下来：常规BCG组71名，延迟接种组66名。常规BCG疫苗接种导致HIV靶向CD 4（+）CCR 5（+）T细胞的系统活化增加3倍（HLA-DR（+）CD 38（+））（出生时为0.25%，延迟接种组为0.08%; P = 0.029），持续至8周龄，此时延迟接种组接种疫苗。在8周时，延迟组的婴儿接种疫苗导致活化的CD 4（+）CCR 5（+）T细胞的类似增加。活化T细胞的增加与外周血单个核细胞中MHC II类反式激活因子（CIITA）、IL 12 RB 1和IFN-α 1转录物水平的增加有关，但先天性细胞的变化很小。BCG疫苗接种可诱导HIV暴露婴儿的免疫变化，包括激活的CCR 5（+）CD 4（+）HIV靶细胞比例增加。这些发现提供了对最佳BCG疫苗接种时机的深入了解，以最大限度地减少暴露婴儿的HIV传播风险，同时保留BCG疫苗接种带来的潜在益处。
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.