Optimization of a human Bacille Calmette-Guérin challenge model: A Tool to Evaluate Antimycobacterial Immunity

Alice Minhinnick; Stephanie Harris; Morven Wilkie; Jonathan Peter; Lisa Stockdale; Zita-Rose Manjaly-Thomas; Samantha Vermaak; Iman Satti; Paul Moss; Helen McShane

doi:10.1093/infdis/jiv482

Optimization of a human Bacille Calmette-Guérin challenge model: A Tool to Evaluate Antimycobacterial Immunity

Alice Minhinnick, Stephanie Harris, Morven Wilkie, Jonathan Peter, Lisa Stockdale, Zita-Rose Manjaly-Thomas, Samantha Vermaak, Iman Satti, Paul Moss, Helen McShane

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Abstract

BACKGROUND: There is an urgent need for an improved tuberculosis vaccine. The lack of a validated correlate of protection slows progress in achieving this goal. A human mycobacterial challenge model, using bacille Calmette-Guérin (BCG) as a surrogate for a Mycobacterium tuberculosis challenge, would facilitate vaccine selection for field efficacy testing. Optimization of this model is required.

METHODS: Healthy BCG-naive adults were assigned to receive intradermal standard-dose BCG SSI (group A), standard-dose BCG TICE (group B), high-dose BCG SSI (group C), and high-dose BCG TICE (group D). Two weeks after BCG challenge, skin biopsy of the challenge site was performed. BCG mycobacterial load was quantified by solid culture and quantitative polymerase chain reaction.

RESULTS: BCG was well tolerated, and reactogenicity was similar between groups, regardless of strain and dose. There was significantly greater recovery of BCG from the high-dose challenge groups, compared with standard-dose challenge. BCG strain did not significantly affect BCG recovery.

CONCLUSIONS: BCG challenge dose affects sensitivity of this model. We have selected high-dose BCG SSI to take forward in future challenge studies. Assessment of candidate tuberculosis vaccine effectiveness with this optimized model could contribute to vaccine selection for efficacy trials.

CLINICAL TRIAL REGISTRATION: NCT02088892.

Original language	English
Pages (from-to)	824-830
Journal	The Journal of Infectious Diseases
Early online date	8 Oct 2015
DOIs	https://doi.org/10.1093/infdis/jiv482
Publication status	Published - 1 Mar 2016

Keywords

BCG
human mycobacterial challenge model
vaccine effectiveness
tuberculosis
anti-mycobacterial immunity

UN SDGs

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

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MinhinnickA2015OptimizationFinal published version, 456 KBLicence: Creative Commons: Attribution (CC BY)

Cite this

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title = "Optimization of a human Bacille Calmette-Gu{\'e}rin challenge model: A Tool to Evaluate Antimycobacterial Immunity",

abstract = "BACKGROUND: There is an urgent need for an improved tuberculosis vaccine. The lack of a validated correlate of protection slows progress in achieving this goal. A human mycobacterial challenge model, using bacille Calmette-Gu{\'e}rin (BCG) as a surrogate for a Mycobacterium tuberculosis challenge, would facilitate vaccine selection for field efficacy testing. Optimization of this model is required.METHODS: Healthy BCG-naive adults were assigned to receive intradermal standard-dose BCG SSI (group A), standard-dose BCG TICE (group B), high-dose BCG SSI (group C), and high-dose BCG TICE (group D). Two weeks after BCG challenge, skin biopsy of the challenge site was performed. BCG mycobacterial load was quantified by solid culture and quantitative polymerase chain reaction.RESULTS: BCG was well tolerated, and reactogenicity was similar between groups, regardless of strain and dose. There was significantly greater recovery of BCG from the high-dose challenge groups, compared with standard-dose challenge. BCG strain did not significantly affect BCG recovery.CONCLUSIONS: BCG challenge dose affects sensitivity of this model. We have selected high-dose BCG SSI to take forward in future challenge studies. Assessment of candidate tuberculosis vaccine effectiveness with this optimized model could contribute to vaccine selection for efficacy trials.CLINICAL TRIAL REGISTRATION: NCT02088892.",

keywords = "BCG, human mycobacterial challenge model, vaccine effectiveness, tuberculosis, anti-mycobacterial immunity",

author = "Alice Minhinnick and Stephanie Harris and Morven Wilkie and Jonathan Peter and Lisa Stockdale and Zita-Rose Manjaly-Thomas and Samantha Vermaak and Iman Satti and Paul Moss and Helen McShane",

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doi = "10.1093/infdis/jiv482",

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AU - Minhinnick, Alice

AU - Harris, Stephanie

AU - Wilkie, Morven

AU - Peter, Jonathan

AU - Stockdale, Lisa

AU - Manjaly-Thomas, Zita-Rose

AU - Vermaak, Samantha

AU - Satti, Iman

AU - Moss, Paul

AU - McShane, Helen

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N2 - BACKGROUND: There is an urgent need for an improved tuberculosis vaccine. The lack of a validated correlate of protection slows progress in achieving this goal. A human mycobacterial challenge model, using bacille Calmette-Guérin (BCG) as a surrogate for a Mycobacterium tuberculosis challenge, would facilitate vaccine selection for field efficacy testing. Optimization of this model is required.METHODS: Healthy BCG-naive adults were assigned to receive intradermal standard-dose BCG SSI (group A), standard-dose BCG TICE (group B), high-dose BCG SSI (group C), and high-dose BCG TICE (group D). Two weeks after BCG challenge, skin biopsy of the challenge site was performed. BCG mycobacterial load was quantified by solid culture and quantitative polymerase chain reaction.RESULTS: BCG was well tolerated, and reactogenicity was similar between groups, regardless of strain and dose. There was significantly greater recovery of BCG from the high-dose challenge groups, compared with standard-dose challenge. BCG strain did not significantly affect BCG recovery.CONCLUSIONS: BCG challenge dose affects sensitivity of this model. We have selected high-dose BCG SSI to take forward in future challenge studies. Assessment of candidate tuberculosis vaccine effectiveness with this optimized model could contribute to vaccine selection for efficacy trials.CLINICAL TRIAL REGISTRATION: NCT02088892.

AB - BACKGROUND: There is an urgent need for an improved tuberculosis vaccine. The lack of a validated correlate of protection slows progress in achieving this goal. A human mycobacterial challenge model, using bacille Calmette-Guérin (BCG) as a surrogate for a Mycobacterium tuberculosis challenge, would facilitate vaccine selection for field efficacy testing. Optimization of this model is required.METHODS: Healthy BCG-naive adults were assigned to receive intradermal standard-dose BCG SSI (group A), standard-dose BCG TICE (group B), high-dose BCG SSI (group C), and high-dose BCG TICE (group D). Two weeks after BCG challenge, skin biopsy of the challenge site was performed. BCG mycobacterial load was quantified by solid culture and quantitative polymerase chain reaction.RESULTS: BCG was well tolerated, and reactogenicity was similar between groups, regardless of strain and dose. There was significantly greater recovery of BCG from the high-dose challenge groups, compared with standard-dose challenge. BCG strain did not significantly affect BCG recovery.CONCLUSIONS: BCG challenge dose affects sensitivity of this model. We have selected high-dose BCG SSI to take forward in future challenge studies. Assessment of candidate tuberculosis vaccine effectiveness with this optimized model could contribute to vaccine selection for efficacy trials.CLINICAL TRIAL REGISTRATION: NCT02088892.

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KW - vaccine effectiveness

KW - tuberculosis

KW - anti-mycobacterial immunity

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ER -

Optimization of a human Bacille Calmette-Guérin challenge model: A Tool to Evaluate Antimycobacterial Immunity

Abstract

Keywords

UN SDGs

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