Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau: A Randomized-controlled Trial
Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau: A Randomized-controlled Trial
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DOI：
10.1093/infdis/jiu508
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发表时间：
2015-03-15
影响因子：
6.4
通讯作者：
Benn, Christine Stabell
中科院分区：
文献类型：
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作者：
Jensen, Kristoffer Jarlov;Larsen, Nanna;Benn, Christine Stabell
背景资料。卡介苗(BCG)似乎具有有益的非特异性作用；早期接种卡介苗可使低出生体重(LBW)新生儿的死亡率降低40%，这主要是因为它能预防败血症和肺炎。在几内亚比绍早期卡介苗和通常延迟卡介苗的LBW婴儿的随机试验中，一个亚组在随机化4周后出血。用天然激动剂刺激Toll样受体(TLR)-2、-4或-7/8或纯化蛋白衍生物(PPD)，检测IL-1β、IL-5、IL-6、IL-10、IL-17、干扰素(干扰素)-γ和肿瘤坏死因子(TNF)-α的水平。在467名婴儿中，卡介苗如预期的那样显著增加了对结核分枝杆菌纯化蛋白衍生物(PPD)的体外细胞因子反应。卡介苗还与对异源先天刺激的反应增加有关，尤其是细胞因子IL-1β、IL-6、肿瘤坏死因子-α和干扰素-γ。免疫四周后，接种卡介苗的婴儿在异种刺激下细胞因子的产生显著增加，特别是辅助性T细胞1型极化和典型的单核细胞来源的促炎细胞因子。卡介苗可以加速新生儿免疫系统的发展，调节对感染和死亡的全面保护。
Background. Bacillus Calmette-Guerin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia.Methods. Within a randomized trial in LBW infants in Guinea-Bissau of early BCG vs the usual postponed BCG, a subgroup was bled 4 weeks after randomization. Levels of interleukin (IL)-1 beta, IL-5, IL-6, IL-10, IL-17, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were measured from whole-blood assays stimulated with innate agonists to Toll-like receptor (TLR)-2, -4 or -7/8, or purified protein derivative (PPD).Results. Among 467 infants, BCG significantly increased the in vitro cytokine responses to purified protein derivative of Mycobacterium tuberculosis (PPD), as expected. BCG was also associated with increased responses to heterologous innate stimulation, particularly of the cytokines IL-1 beta, IL-6, TNF-alpha, and IFN-gamma.Conclusion. Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro-inflammatory cytokines. BCG may accelerate the development of the neonatal immune system, mediating comprehensive protection against infections and mortality.