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

doi:10.1128/CVI.00142-17

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

Medicine

Research output: Contribution to journal › Short survey › peer-review

26 Scopus citations

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 language	English (US)
Article number	e00142
Journal	Clinical and Vaccine Immunology
Volume	24
Issue number	9
DOIs	https://doi.org/10.1128/CVI.00142-17
State	Published - Sep 2017

Keywords

Correlates of immunity
MGIA
Mycobacterial growth inhibition assay
Tuberculosis
Vaccines

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Clinical Biochemistry
Microbiology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/CVI.00142-17

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Brennan, M. J., Tanner, R., Morris, S., Scriba, T. J., Achkar, J. M., Zelmer, A., Hokey, D. A., Izzo, A., Sharpe, S., Williams, A., Penn-Nicholson, A., Erasmus, M., Stylianou, E., Hoft, D. F., McShane, H., & Fletcher, H. A. (2017). The cross-species Mycobacterial Growth Inhibition Assay (MGIA) project, 2010–2014. Clinical and Vaccine Immunology, 24(9), Article e00142. https://doi.org/10.1128/CVI.00142-17

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 2017, 'The cross-species Mycobacterial Growth Inhibition Assay (MGIA) project, 2010–2014', Clinical and Vaccine Immunology, vol. 24, no. 9, e00142. https://doi.org/10.1128/CVI.00142-17

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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.",

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doi = "10.1128/CVI.00142-17",

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AU - Brennan, Michael J.

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AU - Scriba, Thomas J.

AU - Achkar, Jacqueline M.

AU - Zelmer, Andrea

AU - Hokey, David A.

AU - Izzo, Angelo

AU - Sharpe, Sally

AU - Williams, Ann

AU - Penn-Nicholson, Adam

AU - Erasmus, Mzwandile

AU - Stylianou, Elena

AU - Hoft, Daniel F.

AU - McShane, Helen

AU - Fletcher, Helen A.

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N2 - 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.

AB - 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.

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KW - Mycobacterial growth inhibition assay

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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