Kampmann Beate, Tena Gwen N, Mzazi Shumikazi, Eley Brian, Young Douglas B, Levin Michael
School of Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, Republic of South Africa.
Infect Immun. 2004 Nov;72(11):6401-7. doi: 10.1128/IAI.72.11.6401-6407.2004.
Major research efforts are directed towards the development of a better antimycobacterial vaccine. But progress in the field of tuberculosis vaccine development has been hampered by the lack of human in vitro models to assess vaccine immunogenicity and efficacy. New candidate vaccines will have to be evaluated against the existing Mycobacterium bovis BCG "gold standard." It is therefore important to understand the type of immune responses elicited by BCG vaccination to enable comparisons with potential new candidates. We used a novel human in vitro whole-blood model, which measures immune responses to mycobacteria by use of reporter gene-tagged BCG (BCG lux), to study immune responses to BCG vaccination in 50 neonates in a setting in Cape Town, Republic of South Africa, where tuberculosis is endemic. BCG vaccination significantly reduced growth of BCG lux in whole blood (prevaccination median growth ratio [GR], 9.6; range, 1.3 to 24; postvaccination median GR, 3.9; range, 0.6 to 12.2 [P < 0.0001]). Growth of BCG lux was better restricted in vaccinated infants than in unvaccinated age-matched controls (n = 4). BCG vaccination induced significantly higher gamma interferon production in response to BCG lux (P < 0.0001) and to purified protein derivative (P = 0.0001). No significant changes in either growth of BCG lux or cytokine production occurred in an adult control group (n = 6) over the study period. The whole-blood luminescence model detects changes in cellular immune responses to mycobacteria induced by BCG vaccination. It is therefore a useful new tool in studying the immunogenicity of newly developed vaccine candidates prior to large field trials assessing efficacy.
主要的研究工作都致力于研发更好的抗分枝杆菌疫苗。但是，结核病疫苗研发领域的进展因缺乏用于评估疫苗免疫原性和效力的人体体外模型而受阻。新的候选疫苗必须对照现有的牛分枝杆菌卡介苗“金标准”进行评估。因此，了解卡介苗接种引发的免疫反应类型，以便与潜在的新候选疫苗进行比较，这一点很重要。我们使用了一种新型的人体体外全血模型，该模型通过使用报告基因标记的卡介苗（卡介苗发光株）来测量对分枝杆菌的免疫反应，以研究在南非共和国开普敦一个结核病流行地区的50名新生儿中卡介苗接种后的免疫反应。卡介苗接种显著降低了全血中卡介苗发光株的生长（接种前的中位生长率[GR]，9.6；范围，1.3至24；接种后的中位GR，3.9；范围，0.6至12.2[P<0.0001]）。与未接种疫苗的年龄匹配对照组（n = 4）相比，接种疫苗的婴儿对卡介苗发光株生长的限制更好。卡介苗接种后，对卡介苗发光株（P<0.0001）和纯化蛋白衍生物（P = 0.0001）的反应诱导产生了显著更高的γ干扰素。在研究期间，成人对照组（n = 6）中卡介苗发光株的生长或细胞因子产生均未发生显著变化。全血发光模型可检测卡介苗接种诱导的对分枝杆菌的细胞免疫反应变化。因此，在进行评估效力的大型现场试验之前，它是研究新开发候选疫苗免疫原性的一种有用的新工具。
