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.
authors: 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.
authors: Peter
authors: P
authors: Sander
authors: Microbiology Services, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors: Simon
authors: S
authors: Clark
authors: Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
authors: Agnese
authors: A
authors: Petrera
authors: 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.
authors: Cristina
authors: C
authors: Vilaplana
authors: Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
authors: Michael
authors: M
authors: Meuli
authors: Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
authors: Petra
authors: P
authors: Selchow
authors: Deptartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
authors: Andrea
authors: A
authors: Zelmer
authors: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors: Deepa
authors: D
authors: Mohanan
authors: Deptartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
authors: Nuria
authors: N
authors: Andreu
authors: Microbiology Services, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors: Emma
authors: E
authors: Rayner
authors: Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
authors: Michael
authors: M
authors: Dal Molin
authors: Deptartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
authors: Gregory J
authors: GJ
authors: Bancroft
authors: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors: Pål
authors: P
authors: Johansen
authors: 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.
authors: Pere-Joan
authors: PJ
authors: Cardona
authors: Microbiology Services, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors: Ann
authors: A
authors: Williams
authors: Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland; Nationales Zentrum für Mykobakterien, Gloriastrasse 30/32, 8006 Zurich, Switzerland.
authors: Erik C
authors: EC
authors: Böttger
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics*; D003718:Denmark; D004195:Disease Models, Animal; D017353:Gene Deletion; D006099:Granuloma / Q000382:microbiology; D006168:Guinea Pigs; D008168:Lung / Q000382:microbiology / Q000648:ultrastructure; D045726:Metalloproteases / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009163:Mycobacterium bovis / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D045726:Metalloproteases; C568073:Zmp1 protein, Mycobacterium tuberculosis
keywords: BCG; Guinea pig; Live vaccine; Protease; Protection; Safety; Tuberculosis