Brennan Michael J, Tanner Rachel, Morris Sheldon, Scriba Thomas J, Achkar Jacqueline M, Zelmer Andrea, Hokey David A, Izzo Angelo, Sharpe Sally, Williams Ann, Penn-Nicholson Adam, Erasmus Mzwandile, Stylianou Elena, Hoft Daniel F, McShane Helen, Fletcher Helen A
Aeras, Rockville, Maryland, USA.
The Jenner Institute, University of Oxford, Oxford, United Kingdom
Clin Vaccine Immunol. 2017 Sep 5;24(9). doi: 10.1128/CVI.00142-17. Print 2017 Sep.
The development of a functional biomarker assay in the tuberculosis (TB) field would be widely recognized as a major advance in efforts to develop and to test novel TB vaccine candidates efficiently. We present preliminary studies using mycobacterial growth inhibition assays (MGIAs) to detect BCG vaccine responses across species, and we extend this work to determine whether a standardized MGIA can be applied in characterizing new TB vaccines. The comparative MGIA studies reviewed here aimed to evaluate robustness, reproducibility, and ability to reflect responses. In doing so, they have laid the foundation for the development of a MGIA that can be standardized and potentially qualified. A major challenge ahead lies in better understanding the relationships between protection, growth inhibition, and the immune mechanisms involved. The final outcome would be a MGIA that could be used with confidence in TB vaccine trials. We summarize data arising from this project, present a strategy to meet the goals of developing a functional assay for TB vaccine testing, and describe some of the challenges encountered in performing and transferring such assays.
在结核病（TB）领域开发一种功能性生物标志物检测方法将被广泛认为是高效开发和测试新型结核病疫苗候选物的一项重大进展。我们展示了使用分枝杆菌生长抑制试验（MGIA）来检测不同物种对卡介苗（BCG）疫苗反应的初步研究，并将这项工作扩展到确定标准化的MGIA是否可用于表征新型结核病疫苗。本文回顾的比较MGIA研究旨在评估其稳健性、可重复性以及反映反应的能力。通过这样做，它们为开发一种可标准化且可能具备资质的MGIA奠定了基础。未来的一个主要挑战在于更好地理解保护、生长抑制以及所涉及的免疫机制之间的关系。最终成果将是一种可在结核病疫苗试验中放心使用的MGIA。我们总结了该项目产生的数据，提出了一项策略以实现开发用于结核病疫苗检测的功能性检测方法的目标，并描述了在进行和转移此类检测时遇到的一些挑战。
