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Vaccine. 2015 Mar 10;33(11):1353-9. doi: 10.1016/j.vaccine.2015.01.058. Epub 2015 Feb 2.

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

Author information

1
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland; Nationales Zentrum für Mykobakterien, Gloriastrasse 30/32, 8006 Zurich, Switzerland. Electronic address: psander@imm.uzh.ch.
2
Microbiology Services, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
3
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
4
Unitat de Tuberculosi Experimental, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, CIBERES, Badalona, Catalonia, Spain.
5
Deptartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
6
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
7
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland; Nationales Zentrum für Mykobakterien, Gloriastrasse 30/32, 8006 Zurich, Switzerland.

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

PMID:
25657094
DOI:
10.1016/j.vaccine.2015.01.058
[Indexed for MEDLINE]

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