The Cross-Species Mycobacterial Growth Inhibition Assay (MGIA) Project, 2010–2014
Brennan MJ., Tanner R., Morris S., Scriba TJ., Achkar JM., Zelmer A., Hokey DA., Izzo A., Sharpe S., Williams A., Penn-Nicholson A., Erasmus M., Stylianou E., Hoft DF., McShane H., Fletcher HA.
<jats:title>ABSTRACT</jats:title> <jats:p> 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 <jats:named-content content-type="genus-species">Mycobacterium bovis</jats:named-content> 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 <jats:italic>in vivo</jats:italic> 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 <jats:italic>in vivo</jats:italic> protection, <jats:italic>in vitro</jats:italic> 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. </jats:p>