The immune response to BCG vaccination of newborns
The immune response to BCG vaccination of newborns
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DOI：
10.1196/annals.1358.010
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发表时间：
2005-01-01
期刊：
影响因子：
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通讯作者：
Hanekom, WA
中科院分区：
文献类型：
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作者：
Hanekom, WA
本研究的目的是确定目前的疫苗，卡介苗（BCG）诱导的免疫相关的保护对结核病。这些知识对于开发和测试新型结核病疫苗应该是有价值的。从5675名出生时常规接种卡介苗的10周龄南非婴儿中采集血液，进行处理和储存。随后，发现了患有结核病的婴儿-“不受疫苗保护”-以及尽管接触了患有结核病的成年人但仍然保持健康的婴儿-“受疫苗保护”。已经从婴儿的全血样本中引发了对分枝杆菌抗原的回忆性免疫反应;下一步将是取回“未保护”和“保护”婴儿的储存血液，并比较两组中BCG诱导的免疫力。为了指导免疫分析，正在进行各种试点研究，以表征疫苗接种诱导的宿主反应。初步结果表明，卡介苗确实能诱导婴儿产生强有力的CD 8 T细胞反应，并具有产生嘌呤或细胞毒性的潜力。在一些分枝杆菌刺激的全血样品中也发现了FoxP 3 mRNA表达的诱导，这表明存在BCG诱导的调节性CD 4 T细胞。最后，用分枝杆菌抗原刺激全血导致了细胞因子释放的一致模式：大量婴儿产生大量的效应细胞因子干扰素-γ，或大量的调节细胞因子白细胞介素-10，但不是两者兼而有之。因此，将进行测试以确定CD 8或调节性CD 4 T细胞应答以及“离群值”细胞因子应答是否与疫苗诱导的抗结核保护相关。
The aim of this study is to identify immune correlates of protection against tuberculosis induced by the current vaccine, Bacille Calmette Guerin (BCG). This knowledge should be valuable for developing and testing novel tuberculosis vaccines. Blood from 5675 10-week-old South African infants, routinely vaccinated with BCG at birth, was collected, processed, and stored. Subsequently, infants who have developed tuberculosis disease-"not protected by the vaccine"-and infants who have remained healthy despite exposure to adults with tuberculosis-"protected by the vaccine"-have been identified. Recall immune responses to mycobacterial antigens in whole blood samples from the infants have been elicited; the next step will be to retrieve stored blood of "unprotected" and "protected" infants and compare immunity induced by BCG in the two groups. To guide the immune analysis, various pilot studies are being conducted to characterize the vaccination-induced host response. Preliminary results indicate that BCG does indeed induce a potent CD8 T-cell response, with cytokine-producing or cytotoxic potential, in infants. An induction of FoxP3 mRNA expression in some mycobacteria-stimulated whole-blood samples is also being found, which suggests the presence of BCG-induced regulatory CD4 T cells. Finally, stimulation of whole blood with mycobacterial antigens has resulted in a consistent pattern of cytokine release: significant numbers of infants make either large amounts of the effector cytokine interferon-gamma, or large amounts of the regulatory cytokine interleukin-10, but not both. Tests will, therefore, be made to determine whether CD8 or regulatory CD4 T-cell responses, as well as "outlier" cytokine responses, are associated with vaccination-induced protection against tuberculosis.