Weir Rosemary E, Fine Paul E M, Floyd Sian, Stenson Sally, Stanley Carolynne, Branson Keith, Britton Warwick J, Huygen Kris, Singh Mahavir, Black Gillian, Dockrell Hazel M
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Tuberculosis (Edinb). 2008 Jan;88(1):31-8. doi: 10.1016/j.tube.2007.10.001.
An increase in interferon-gamma (IFN-gamma) production to Mycobacterium tuberculosis purified protein derivative (Mtb PPD), as measured in the cultured diluted whole blood assay, is one indicator of a protective immune response to BCG vaccine. We have explored the potential for this assay to be improved by measuring IFN-gamma responses to more defined antigens of M. tuberculosis (short-term and mid-term culture filtrates, ESAT-6, 38 kDa), Mycobacterium bovis (MPB70), M. bovis BCG (Antigen 85) and Mycobacterium leprae (35 kDa), in UK teenagers before and 1 year after BCG vaccination (or no vaccination as controls). There was a significant increase in response to the culture filtrates post-vaccination, but this was no greater than that to Mtb PPD. Many teenagers responded to the purified antigens, in particular to Antigen 85, prior to vaccination, and BCG vaccination could only augment this pre-existing response to a limited extent; prior exposure to environmental mycobacteria can thus induce cross-reactive responses to antigens which complicate interpretation of in vitro assays of vaccine response. In contrast, ESAT-6 was recognised by only one teenager prior to vaccination, and, as expected, responses were not boosted by BCG. We therefore conclude that Mtb PPD is the antigen preparation of choice for assessing the immunogenicity of BCG vaccination.
在培养的稀释全血试验中,测量到的针对结核分枝杆菌纯化蛋白衍生物(Mtb PPD)的干扰素-γ(IFN-γ)产量增加是对卡介苗产生保护性免疫反应的一个指标。我们探讨了通过测量英国青少年在接种卡介苗前和接种后1年(或不接种作为对照)对结核分枝杆菌更明确抗原(短期和中期培养滤液、ESAT-6、38 kDa)、牛分枝杆菌(MPB70)、卡介苗(抗原85)和麻风分枝杆菌(35 kDa)的IFN-γ反应来改进该试验的可能性。接种疫苗后对培养滤液的反应显著增加,但不超过对Mtb PPD的反应。许多青少年在接种疫苗前对纯化抗原,特别是对抗原85有反应,卡介苗接种只能在有限程度上增强这种预先存在的反应;因此,先前接触环境分枝杆菌可诱导对抗原的交叉反应,这使疫苗反应的体外试验解释复杂化。相比之下,ESAT-6在接种疫苗前仅被一名青少年识别,并且如预期的那样,卡介苗并未增强反应。因此,我们得出结论,Mtb PPD是评估卡介苗免疫原性的首选抗原制剂。