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


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. ISSN 0264-410X DOI: https://doi.org/10.1016/j.vaccine.2015.01.058

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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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 25657094
Web of Science ID: 350925600009
URI: http://researchonline.lshtm.ac.uk/id/eprint/2111804

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