Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation.
Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation.
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DOI：
10.1016/j.vaccine.2019.11.060
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发表时间：
2020-02-24
期刊：
影响因子：
5.5
通讯作者：
Levy O
中科院分区：
文献类型：
--
作者：
Angelidou A;Conti MG;Diray-Arce J;Benn CS;Shann F;Netea MG;Liu M;Potluri LP;Sanchez-Schmitz G;Husson R;Ozonoff A;Kampmann B;van Haren SD;Levy O
卡介苗（BCG）是结核病减毒活疫苗，在地球仪不同的条件下生产，产生的制剂可能具有不同的临床疗效。活BCG的天然免疫识别有助于免疫原性，表明BCG活力的差异可能有助于许可制剂的不同活性。我们比较了BCG丹麦（DEN）、日本（JPN）、印度（IND）、保加利亚（BUL）和美国（USA）在体外a）通过菌落形成单位（CFU）、分枝杆菌膜完整性和RNA含量测量的活力，和B）新生儿脐带和成人外周血中细胞因子/趋化因子的产生。在培养时，相对生长为BCG-USA > JPN >> DEN > BUL = INDJCG-IND和-BUL在7 H9培养基中表现出比BCG-JPN低>1000倍的生长，并且在商业Middlebrook 7 H11培养基中表现出比BCG-JPN低>10倍的生长。与其他BCG相比，BCG-IND在全血中表现出显著降低的膜完整性、较低的RNA含量和较弱的IFN-c诱导活性。BCG诱导的全血细胞因子在年龄、疫苗配方和浓度方面存在显著差异。BCG诱导的细胞因子产生与CFU相关，表明分枝杆菌的生存能力可能有助于BCG诱导的免疫反应。许可的BCG疫苗在活分枝杆菌的含量方面存在明显差异，这可能有助于先天性和适应性免疫的制剂依赖性激活以及不同的保护作用。
Bacille Calmette-Guérin (BCG), the live attenuated tuberculosis vaccine, is manufactured under different conditions across the globe generating formulations that may differ in clinical efficacy. Innate immune recognition of live BCG contributes to immunogenicity suggesting that differences in BCG viability may contribute to divergent activity of licensed formulations. We compared BCG-Denmark (DEN), -Japan (JPN), -India (IND), -Bulgaria (BUL) and -USA in vitro with respect to a) viability as measured by colony-forming units (CFU), mycobacterial membrane integrity, and RNA content, and b) cytokine/chemokine production in newborn cord and adult peripheral blood. Upon culture, relative growth was BCG-USA > JPN >> DEN > BUL = IND. BCG-IND and -BUL demonstrated >1000-fold lower growth than BCG-JPN in 7H9 medium and >10-fold lower growth in commercial Middlebrook 7H11 medium. BCG-IND demonstrated significantly decreased membrane integrity, lower RNA content, and weaker IFN-c inducing activity in whole blood compared to other BCGs. BCG-induced whole blood cytokines differed significantly by age, vaccine formulation and concentration. BCG-induced cytokine production correlated with CFU, suggesting that mycobacterial viability may contribute to BCG-induced immune responses. Licensed BCG vaccines differ markedly in their content of viable mycobacteria possibly contributing to formulation-dependent activation of innate and adaptive immunity and distinct protective effects.
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来自哈萨克斯坦的不同来源的芽孢杆菌Callette-Guérin（BCG）疫苗儿童的比较结核病（TB）预防效果。
影响因子：
3.7
作者：
Favorov M;Ali M;Tursunbayeva A;Aitmagambetova I;Kilgore P;Ismailov S;Chorba T
通讯作者：
Chorba T
影响因子：
3.2
作者：
Berendsen, Mike L. T.;Oland, Christian Bjerregard;Aaby, Peter
通讯作者：
Aaby, Peter
DOI：
10.1164/rccm.201003-0334oc
发表时间：
2010-10-15
影响因子：
24.7
作者：
Kagina, Benjamin M. N.;Abel, Brian;Hanekom, Willem A.
通讯作者：
Hanekom, Willem A.
影响因子：
3.6
作者：
KROGER, L;BRANDER, E;KATILA, ML
通讯作者：
KATILA, ML
Calmette-Guérin（BCG）疫苗：全球需求和供应平衡评估。
影响因子：
5.5
作者：
Cernuschi T;Malvolti S;Nickels E;Friede M
通讯作者：
Friede M