Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis

Peter Sander; Simon Clark; Agnese Petrera; Cristina Vilaplana; Michael Meuli; Petra Selchow; Andrea Zelmer; Deepa Mohanan; Nuria Andreu; Emma Rayner; Michael Dal Molin; Gregory J. Bancroft; Pål Johansen; Pere Joan Cardona; Ann Williams; Erik C. Böttger

doi:10.1016/j.vaccine.2015.01.058

Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis

Peter Sander^*, Simon Clark, Agnese Petrera, Cristina Vilaplana, Michael Meuli, Petra Selchow, Andrea Zelmer, Deepa Mohanan, Nuria Andreu, Emma Rayner, Michael Dal Molin, Gregory J. Bancroft, Pål Johansen, Pere Joan Cardona, Ann Williams, Erik C. Böttger

^*Corresponding author for this work

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Abstract

Having demonstrated previously that deletion of zinc metalloprotease zmp1 in Mycobacterium bovis BCG increased immunogenicity of BCG vaccines, we here investigated the protective efficacy of BCG zmp1 deletion mutants in a guinea pig model of tuberculosis infection. zmp1 deletion mutants of BCG provided enhanced protection by reducing the bacterial load of tubercle bacilli in the lungs of infected guinea pigs. The increased efficacy of BCG due to zmp1 deletion was demonstrated in both BCG Pasteur and BCG Denmark indicating that the improved protection by zmp1 deletion is independent from the BCG sub-strain. In addition, unmarked BCG δzmp1 mutant strains showed a better safety profile in a CB-17 SCID mouse survival model than the parental BCG strains. Together, these results support the further development of BCG δzmp1 for use in clinical trials.

Original language	English
Pages (from-to)	1353-1359
Number of pages	7
Journal	Vaccine
Volume	33
Issue number	11
DOIs	https://doi.org/10.1016/j.vaccine.2015.01.058
Publication status	Published - 10 Mar 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ltd.

Keywords

BCG
Guinea pig
Live vaccine
Protease
Protection
Safety
Tuberculosis

UN SDGs

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

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10.1016/j.vaccine.2015.01.058

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Sander, P., Clark, S., Petrera, A., Vilaplana, C., Meuli, M., Selchow, P., Zelmer, A., Mohanan, D., Andreu, N., Rayner, E., Dal Molin, M., Bancroft, G. J., Johansen, P., Cardona, P. J., Williams, A., & Böttger, E. C. (2015). Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis. Vaccine, 33(11), 1353-1359. https://doi.org/10.1016/j.vaccine.2015.01.058

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title = "Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis",

abstract = "Having demonstrated previously that deletion of zinc metalloprotease zmp1 in Mycobacterium bovis BCG increased immunogenicity of BCG vaccines, we here investigated the protective efficacy of BCG zmp1 deletion mutants in a guinea pig model of tuberculosis infection. zmp1 deletion mutants of BCG provided enhanced protection by reducing the bacterial load of tubercle bacilli in the lungs of infected guinea pigs. The increased efficacy of BCG due to zmp1 deletion was demonstrated in both BCG Pasteur and BCG Denmark indicating that the improved protection by zmp1 deletion is independent from the BCG sub-strain. In addition, unmarked BCG δzmp1 mutant strains showed a better safety profile in a CB-17 SCID mouse survival model than the parental BCG strains. Together, these results support the further development of BCG δzmp1 for use in clinical trials.",

keywords = "BCG, Guinea pig, Live vaccine, Protease, Protection, Safety, Tuberculosis",

author = "Peter Sander and Simon Clark and Agnese Petrera and Cristina Vilaplana and Michael Meuli and Petra Selchow and Andrea Zelmer and Deepa Mohanan and Nuria Andreu and Emma Rayner and {Dal Molin}, Michael and Bancroft, {Gregory J.} and P{\aa}l Johansen and Cardona, {Pere Joan} and Ann Williams and B{\"o}ttger, {Erik C.}",

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doi = "10.1016/j.vaccine.2015.01.058",

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Sander, P, Clark, S, Petrera, A, Vilaplana, C, Meuli, M, Selchow, P, Zelmer, A, Mohanan, D, Andreu, N, Rayner, E, Dal Molin, M, Bancroft, GJ, Johansen, P, Cardona, PJ, Williams, A & Böttger, EC 2015, 'Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis', Vaccine, vol. 33, no. 11, pp. 1353-1359. https://doi.org/10.1016/j.vaccine.2015.01.058

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AU - Sander, Peter

AU - Clark, Simon

AU - Petrera, Agnese

AU - Vilaplana, Cristina

AU - Meuli, Michael

AU - Selchow, Petra

AU - Zelmer, Andrea

AU - Mohanan, Deepa

AU - Andreu, Nuria

AU - Rayner, Emma

AU - Dal Molin, Michael

AU - Bancroft, Gregory J.

AU - Johansen, Pål

AU - Cardona, Pere Joan

AU - Williams, Ann

AU - Böttger, Erik C.

PY - 2015/3/10

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N2 - Having demonstrated previously that deletion of zinc metalloprotease zmp1 in Mycobacterium bovis BCG increased immunogenicity of BCG vaccines, we here investigated the protective efficacy of BCG zmp1 deletion mutants in a guinea pig model of tuberculosis infection. zmp1 deletion mutants of BCG provided enhanced protection by reducing the bacterial load of tubercle bacilli in the lungs of infected guinea pigs. The increased efficacy of BCG due to zmp1 deletion was demonstrated in both BCG Pasteur and BCG Denmark indicating that the improved protection by zmp1 deletion is independent from the BCG sub-strain. In addition, unmarked BCG δzmp1 mutant strains showed a better safety profile in a CB-17 SCID mouse survival model than the parental BCG strains. Together, these results support the further development of BCG δzmp1 for use in clinical trials.

AB - Having demonstrated previously that deletion of zinc metalloprotease zmp1 in Mycobacterium bovis BCG increased immunogenicity of BCG vaccines, we here investigated the protective efficacy of BCG zmp1 deletion mutants in a guinea pig model of tuberculosis infection. zmp1 deletion mutants of BCG provided enhanced protection by reducing the bacterial load of tubercle bacilli in the lungs of infected guinea pigs. The increased efficacy of BCG due to zmp1 deletion was demonstrated in both BCG Pasteur and BCG Denmark indicating that the improved protection by zmp1 deletion is independent from the BCG sub-strain. In addition, unmarked BCG δzmp1 mutant strains showed a better safety profile in a CB-17 SCID mouse survival model than the parental BCG strains. Together, these results support the further development of BCG δzmp1 for use in clinical trials.

KW - BCG

KW - Guinea pig

KW - Live vaccine

KW - Protease

KW - Protection

KW - Safety

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JF - Vaccine

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ER -

Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis

Abstract

Bibliographical note

Keywords

UN SDGs

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