The cross-species Mycobacterial Growth Inhibition Assay (MGIA) project, 2010–2014

Michael J. Brennan, Rachel Tanner*, Sheldon Morris, Thomas J. Scriba, Jacqueline M. Achkar, Andrea Zelmer, David A. Hokey, Angelo Izzo, Sally Sharpe, Ann Williams, Adam Penn-Nicholson, Mzwandile Erasmus, Elena Stylianou, Daniel F. Hoft, Helen McShane, Helen A. Fletcher

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

17 Citations (Scopus)

Abstract

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 Mycobacterium bovis 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 in vivo 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 in vivo protection, in vitro 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.

Original languageEnglish
Article numbere00142
JournalClinical and Vaccine Immunology
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 2017

Bibliographical note

Funding Information:
We thank the U.S. FDA (FDA grant IU18FD004012-01) and Aeras for financial support. The research leading to some of these results has also received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement 312661 (European Research Infrastructures for Poverty Related Diseases), the European Union Horizon 2020 research and innovation program under grant agreement 643381, the Universities Federation for Animal Welfare, the Wellcome Trust, and the Bill and Melinda Gates Foundation. We declare that we have no competing interests.

Publisher Copyright:
© 2017 Brennan et al.

Keywords

  • Correlates of immunity
  • MGIA
  • Mycobacterial growth inhibition assay
  • Tuberculosis
  • Vaccines

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