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Vaccine Detail
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BCG mutant secreting listeriolysin |
| Vaccine Information |
- Vaccine Name: BCG mutant secreting listeriolysin
- Target Pathogen: Mycobacterium tuberculosis
- Target Disease: Tuberculosis
- Vaccine Ontology ID: VO_0000603
- Type: Subunit vaccine
- Antigen: The tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guérin (BCG) was equipped with the membrane-perforating listeriolysin (Hly) of Listeria monocytogenes (Grode et al., 2005).
- Preparation: BCG pAT261:Hly and BCG pMV306:Hly with actively-secreted hemolysin were constructed using chromosomal integration of a mycobacterial shuttle vector (pAT261 or PMV306) or by episomal plasmid replication, respectively (Hess et al., 1998; Hess et al., 1999). These plasmids were introduced into M. bovis BCG using standard electroporation. Fusion proteins were isolated and separated (Hess et al., 1998). In later studies, the fusion proteins were expressed by S. typhimurium strain SL7207's aroA pathway (Hess et al., 1999).
- Virulence: The r-BCG has decreased intracellular persistence versus the parental BCG strain (Hess et al., 1999). Mycobacterial CFUs from infected macrophages were used to ascertain survival of BCG pAT261:Hly and BCG pMV306:Hly in host macrophages. Intracelluar survival of the BCG pMV306:Hly strain was reduced at day 1 post-infection, and viable BCG pAT261:Hly were not detected in J774A.1 macrophages at 15 days post-infection. Furthermore, the recombinant strains failed to escape from the phagosome of macrophages (Hess et al., 1998).
- Description: A recombinant BCG strain was constructed to secrete a pore-forming sulfhydrul-activated cytolysin (listeriolysin or Hly) from Listeria monocytogenes. Listeriolysin assists Listeria in escaping from the phagosome into the cytosol of the infected host cell. The study shows that Hly secretion improves stimulation of CD8 T cells (by pronounced MHC class I processing and delivery) in recombinant BCG (Hess et al., 1999).
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| Host Response |
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| References |
Grode et al., 2005: Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Nasser Eddine A, Mann P, Goosmann C, Bandermann S, Smith D, Bancroft GJ, Reyrat JM, van Soolingen D, Raupach B, Kaufmann SH. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. The Journal of clinical investigation. 2005; 115(9); 2472-2479. [PubMed: 16110326].
Hess et al., 1998: Hess J, Miko D, Catic A, Lehmensiek V, Russell DG, Kaufmann SH. Mycobacterium bovis Bacille Calmette-Guerin strains secreting listeriolysin of Listeria monocytogenes. Proceedings of the National Academy of Sciences of the United States of America. 1998 Apr 28; 95(9); 5299-304. [PubMed: 9560270].
Hess et al., 1999: Hess J, Kaufmann SH. Live antigen carriers as tools for improved anti-tuberculosis vaccines. FEMS immunology and medical microbiology. 1999 Feb; 23(2); 165-73. [PubMed: 10076914 ].
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