Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb)

Leanne Marsay; Magali Matsumiya; Rachel Tanner; Hazel Poyntz; Kristin L. Griffiths; Elena Stylianou; Philip D. Marsh; Ann Williams; Sally Sharpe; Helen Fletcher; Helen McShane

doi:10.1016/j.tube.2013.04.007

Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb)

Leanne Marsay^*, Magali Matsumiya, Rachel Tanner, Hazel Poyntz, Kristin L. Griffiths, Elena Stylianou, Philip D. Marsh, Ann Williams, Sally Sharpe, Helen Fletcher, Helen McShane

^*Corresponding author for this work

Research & Development Institute Scientific Leaders

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

Development of an improved vaccine against tuberculosis (TB) is hindered by the lack of a surrogate of protection. Efficacy of new TB vaccines in humans can only be evaluated by expensive and time consuming efficacy trials within TB endemic areas. It is critical that vaccines with the greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope that these in-vitro functional assays will correlate with protection, which could aid in the selection of the best vaccine candidates. The present study describes the use of the BACTEC system to perform MGIAs in mice. We demonstrate reproducible mycobacterial growth inhibition in splenocytes from BCG immunised mice compared with unimmunised mice (P < 0.023), which corresponded with in-vivo efficacy against Mycobacterium tuberculosis (M. tb) challenge. Microarray data showed extensive differential gene expression in splenocyte responses to ex-vivo BCG stimulation between unimmunised and BCG-immunised mice. T_H1 responses, including IFN-γ, nitric oxide synthase (NOS2) and Interleukin -17 (IL-17) expression were enhanced in BCG immunised mice, indicating a possible mechanism for mycobacterial growth inhibition. Further investigation into whether the BACTEC MGIA can be used as a surrogate of protection in humans and preclinical animal models is now warranted.

Original language	English
Pages (from-to)	551-557
Number of pages	7
Journal	Tuberculosis
Volume	93
Issue number	5
DOIs	https://doi.org/10.1016/j.tube.2013.04.007
Publication status	Published - Sept 2013

Bibliographical note

Funding Information:
This work was equally funded by the Oxford Biomedical Research Centre and the Health Protection Agency . The study sponsors had no input into the study design, in the collection, analysis and interpretation of data.

Keywords

BCG
Gene expression
In-vitro assay
Tuberculosis
Vaccine

UN SDGs

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

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10.1016/j.tube.2013.04.007

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title = "Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb)",

abstract = "Development of an improved vaccine against tuberculosis (TB) is hindered by the lack of a surrogate of protection. Efficacy of new TB vaccines in humans can only be evaluated by expensive and time consuming efficacy trials within TB endemic areas. It is critical that vaccines with the greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope that these in-vitro functional assays will correlate with protection, which could aid in the selection of the best vaccine candidates. The present study describes the use of the BACTEC system to perform MGIAs in mice. We demonstrate reproducible mycobacterial growth inhibition in splenocytes from BCG immunised mice compared with unimmunised mice (P < 0.023), which corresponded with in-vivo efficacy against Mycobacterium tuberculosis (M. tb) challenge. Microarray data showed extensive differential gene expression in splenocyte responses to ex-vivo BCG stimulation between unimmunised and BCG-immunised mice. TH1 responses, including IFN-γ, nitric oxide synthase (NOS2) and Interleukin -17 (IL-17) expression were enhanced in BCG immunised mice, indicating a possible mechanism for mycobacterial growth inhibition. Further investigation into whether the BACTEC MGIA can be used as a surrogate of protection in humans and preclinical animal models is now warranted.",

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author = "Leanne Marsay and Magali Matsumiya and Rachel Tanner and Hazel Poyntz and Griffiths, {Kristin L.} and Elena Stylianou and Marsh, {Philip D.} and Ann Williams and Sally Sharpe and Helen Fletcher and Helen McShane",

note = "Funding Information: This work was equally funded by the Oxford Biomedical Research Centre and the Health Protection Agency . The study sponsors had no input into the study design, in the collection, analysis and interpretation of data. ",

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AU - Marsay, Leanne

AU - Matsumiya, Magali

AU - Tanner, Rachel

AU - Poyntz, Hazel

AU - Griffiths, Kristin L.

AU - Stylianou, Elena

AU - Marsh, Philip D.

AU - Williams, Ann

AU - Sharpe, Sally

AU - Fletcher, Helen

AU - McShane, Helen

N1 - Funding Information: This work was equally funded by the Oxford Biomedical Research Centre and the Health Protection Agency . The study sponsors had no input into the study design, in the collection, analysis and interpretation of data.

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N2 - Development of an improved vaccine against tuberculosis (TB) is hindered by the lack of a surrogate of protection. Efficacy of new TB vaccines in humans can only be evaluated by expensive and time consuming efficacy trials within TB endemic areas. It is critical that vaccines with the greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope that these in-vitro functional assays will correlate with protection, which could aid in the selection of the best vaccine candidates. The present study describes the use of the BACTEC system to perform MGIAs in mice. We demonstrate reproducible mycobacterial growth inhibition in splenocytes from BCG immunised mice compared with unimmunised mice (P < 0.023), which corresponded with in-vivo efficacy against Mycobacterium tuberculosis (M. tb) challenge. Microarray data showed extensive differential gene expression in splenocyte responses to ex-vivo BCG stimulation between unimmunised and BCG-immunised mice. TH1 responses, including IFN-γ, nitric oxide synthase (NOS2) and Interleukin -17 (IL-17) expression were enhanced in BCG immunised mice, indicating a possible mechanism for mycobacterial growth inhibition. Further investigation into whether the BACTEC MGIA can be used as a surrogate of protection in humans and preclinical animal models is now warranted.

AB - Development of an improved vaccine against tuberculosis (TB) is hindered by the lack of a surrogate of protection. Efficacy of new TB vaccines in humans can only be evaluated by expensive and time consuming efficacy trials within TB endemic areas. It is critical that vaccines with the greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope that these in-vitro functional assays will correlate with protection, which could aid in the selection of the best vaccine candidates. The present study describes the use of the BACTEC system to perform MGIAs in mice. We demonstrate reproducible mycobacterial growth inhibition in splenocytes from BCG immunised mice compared with unimmunised mice (P < 0.023), which corresponded with in-vivo efficacy against Mycobacterium tuberculosis (M. tb) challenge. Microarray data showed extensive differential gene expression in splenocyte responses to ex-vivo BCG stimulation between unimmunised and BCG-immunised mice. TH1 responses, including IFN-γ, nitric oxide synthase (NOS2) and Interleukin -17 (IL-17) expression were enhanced in BCG immunised mice, indicating a possible mechanism for mycobacterial growth inhibition. Further investigation into whether the BACTEC MGIA can be used as a surrogate of protection in humans and preclinical animal models is now warranted.

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Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb)

Abstract

Bibliographical note

Keywords

UN SDGs

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