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首页> 外文期刊>Vaccine >The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda
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The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda

机译：BCG疫苗株对乌干达未来人群的分枝杆菌特异性和非特异性免疫反应的影响

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Background: Globally, BCG vaccination varies in efficacy and has some non-specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses. Methods: Infants from the Entebbe Mother and Baby Study (ISRCTN32849447) who received BCG-Russia, BCG-Bulgaria or BCG-Denmark at birth, were analysed by BCG strain group. At one year, interferon-gamma (IFN-gamma), interleukin (IL)-5, IL-13 and IL-10 responses to mycobacteria-specific antigens (crude culture filtrate proteins and antigen 85) and non-mycobacterial stimuli (tetanus toxoid and phytohaemagglutinin) were measured using ELISA. Cytokine responses, scar frequency, BCG associated adverse event frequency and mortality rates were compared across groups, with adjustments for potential con-founders. Results: Both specific and non-specific IFN-gamma, IL-13 and IL-10 responses in 1341 infants differed between BCG strain groups including in response to stimulation with tetanus toxoid. BCG-Denmark immunised infants showed the highest cytokine responses. The proportion of infants who scarred differed significantly, with BCG scars occurring in 52.2%, 64.1% and 92.6% of infants immunised with BCG Russia, BCG-Bulgaria and BCG-Denmark, respectively (p < 0.001). Scarred infants had higher IFN-gamma and IL-13 responses to mycobacterial antigens only than infants without a scar. The BCG-Denmark group had the highest frequency of adverse events (p = 0.025). Mortality differences were not significant. Conclusions: Both specific and non-specific immune responses to the BCG vaccine differ by strain. Scarring after BCG vaccination is also strain-dependent and is associated with higher IFN-gamma and IL-13 responses to mycobacterial antigens. The choice of BCG strain may be an important factor and should be evaluated when testing novel vaccine strategies that employ BCG in prime-boost sequences, or as a vector for other vaccine antigens
机译：背景：全球范围内，卡介苗接种的功效各不相同，并具有一些非特异性的保护作用。以前比较BCG菌株的研究规模很小，免疫结果很少或没有，并且仅比较了结核病特异性应答。我们旨在评估大型婴儿队列中针对不同BCG菌株的特异性和非特异性免疫反应，并进一步评估BCG菌株，瘢痕形成和细胞因子反应之间的关系。方法：对来自恩德培母婴研究（ISRCTN32849447）的婴儿在出生时接受BCG-俄罗斯，BCG-保加利亚或BCG-丹麦的婴儿进行BCG菌株组分析。一年后，干扰素-γ（IFN-γ），白介素（IL）-5，IL-13和IL-10对分枝杆菌特异性抗原（粗培养滤液蛋白和抗原85）和非分枝杆菌刺激物（破伤风类毒素）产生反应和ELISA进行测定。比较了各组的细胞因子反应，疤痕频率，BCG相关不良事件发生频率和死亡率，并对潜在的混杂因素进行了调整。结果：1341例婴儿的特异性和非特异性IFN-γ，IL-13和IL-10应答在BCG菌株组之间有所不同，包括对破伤风类毒素刺激的应答。经BCG-丹麦免疫的婴儿显示出最高的细胞因子反应。发生疤痕的婴儿比例差异显着，在接受BCG俄罗斯，BCG保加利亚和BCG丹麦免疫的婴儿中，BCG疤痕分别占52.2％，64.1％和92.6％（p <0.001）。与没有疤痕的婴儿相比，结疤的婴儿仅对分枝杆菌抗原具有更高的IFN-γ和IL-13反应。 BCG-丹麦组发生不良事件的频率最高（p = 0.025）。死亡率差异不显着。结论：针对BCG疫苗的特异性和非特异性免疫反应因菌株而异。 BCG疫苗接种后的瘢痕形成还取决于菌株，并且与对分枝杆菌抗原的更高的IFN-γ和IL-13反应有关。 BCG菌株的选择可能是一个重要因素，在测试在初免-加强序列中使用BCG或作为其他疫苗抗原的载体的新型疫苗策略时，应进行评估

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