The Influence of Bacille Calmette-Guerin Vaccine Strain on the Immune Response against Tuberculosis A Randomized Trial
The Influence of Bacille Calmette-Guerin Vaccine Strain on the Immune Response against Tuberculosis A Randomized Trial
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DOI：
10.1164/rccm.201104-0714oc
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发表时间：
2012-01-15
影响因子：
24.7
通讯作者：
Curtis, Nigel
中科院分区：
文献类型：
--
作者：
Ritz, Nicole;Dutta, Binita;Curtis, Nigel
理由：每年约有1亿剂卡介苗用于预防结核病。世界上有20多种不同基因的BCG疫苗株在使用。以往的研究表明，BCG疫苗株影响免疫应答和对结核病的保护。目前的数据，其中BCG疫苗株诱导最佳的免疫反应在human.Objectives：比较三种不同的BCG疫苗株给予婴儿在birth.Methods的免疫反应：新生儿在三级妇女医院进行了免疫接种，在出生时与三个BCG疫苗株之一。分层随机化根据母亲的出生区域wasness. Measures和主要结果：存在的分枝杆菌特异性多功能的CD 4 T细胞的流式细胞术测定免疫后10周。在209名接受免疫接种的婴儿中，164名婴儿的数据被纳入最终分析（BCG-丹麦，n = 54; BCG-日本，n = 54; BCG-俄罗斯，n = 57）。丹麦卡介菌（0.013%）和日本卡介菌（0.016%）免疫组的多功能性CD 4 T细胞比例显著高于俄罗斯卡介菌（0.007%）（分别为P = 0.018和P = 0.003）。日本卡介苗免疫的新生儿分泌的Th 1细胞因子浓度较高;丹麦卡介苗免疫的新生儿分泌的表达CD 107的细胞毒性CD 4 T细胞比例较高。用BCG丹麦或BCG日本免疫诱导更高频率的分枝杆菌特异性多功能和细胞毒性T细胞和更高浓度的Th 1细胞因子。这些发现对全球抗结核免疫政策和未来的结核疫苗试验具有潜在的重要意义。
Rationale: Approximately 100 million doses of bacille Calmette-Guerin (BCG) vaccine are given each year to protect against tuberculosis (TB). More than 20 genetically distinct BCG vaccine strains are in use worldwide. Previous studies suggest that BCG vaccine strain influences the immune response and protection against TB. Current data on which BCG vaccine strain induces the optimal immune response in humans are insufficient.Objectives: To compare the immune response to three different BCG vaccine strains given to infants at birth.Methods: Newborn infants in a tertiary women's hospital were immunized at birth with one of three BCG vaccine strains. A stratified randomization according to the mother's region of birth was used.Measurements and Main Results: The presence of mycobacterial-specific polyfunctional CD4 T cells measured by flow cytometry 10 weeks after immunization. Of the 209 infants immunized, data from 164 infants were included in the final analysis(BCG-Denmark, n = 54; BCG-Japan, n = 54; BCG-Russia, n = 57). The proportion of polyfunctional CD4 T cells was significantly higher in infants immunized with BCG-Denmark (0.013%) or BCG-Japan (0.016%) than with BCG-Russia (0.007%) (P = 0.018 and P = 0.003, respectively). Infants immunized with BCG-Japan had higher concentrations of secreted Th1 cytokines; infants immunized with BCG-Denmark had higher proportions of CD107-expressing cytotoxic CD4 T cells.Conclusions: There are significant differences in the immune response induced by different BCG vaccine strains in newborn infants. Immunization with BCG-Denmark or BCG-Japan induced higher frequencies of mycobacterial-specific polyfunctional and cytotoxic T cells and higher concentrations of Th1 cytokines. These findings have potentially important implications for global antituberculosis immunization policies and future tuberculosis vaccine trials.