Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin.


Grode, L; Seiler, P; Baumann, S; Hess, J; Brinkmann, V; Eddine, AN; Mann, P; Goosmann, C; Bandermann, S; Smith, D; Bancroft, GJ; Reyrat, JM; van Soolingen, D; Raupach, B; Kaufmann, SH; (2005) Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin. The Journal of clinical investigation, 115 (9). pp. 2472-2479. ISSN 0021-9738 DOI: 10.1172/JCI24617

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Abstract

The tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guérin (BCG) was equipped with the membrane-perforating listeriolysin (Hly) of Listeria monocytogenes, which was shown to improve protection against Mycobacterium tuberculosis. Following aerosol challenge, the Hly-secreting recombinant BCG (hly rBCG) vaccine was shown to protect significantly better against aerosol infection with M. tuberculosis than did the parental BCG strain. The isogenic, urease C-deficient hly rBCG (DeltaureC hly rBCG) vaccine, providing an intraphagosomal pH closer to the acidic pH optimum for Hly activity, exhibited still higher vaccine efficacy than parental BCG. DeltaureC hly+ rBCG also induced profound protection against a member of the M. tuberculosis Beijing/W genotype family while parental BCG failed to do so consistently. Hly not only promoted antigen translocation into the cytoplasm but also apoptosis of infected macrophages. We concluded that superior vaccine efficacy of DeltaureC hly+ rBCG as compared with parental BCG is primarily based on improved cross-priming, which causes enhanced T cell-mediated immunity.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: TB Centre
Vaccine Centre
PubMed ID: 16110326
Web of Science ID: 231708500024
URI: http://researchonline.lshtm.ac.uk/id/eprint/13163

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