Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Live antigen carriers as tools for improved anti-tuberculosis vaccines.
FEMS Immunol Med Microbiol. 1999 Feb;23(2):165-73. Unique Identifier : AIDSLINE MED/99174532 Hess J; Kaufmann SH; Max-Planck-Institute for Infection Biology, Department of; Immunology, Berlin, Germany. Hess@mpiib-berlin.mpg.de
Abstract:
Recombinant (r) Mycobacterium bovis BCG strains have been constructed which secrete biologically active listeriolysin (Hly) fusion protein of Listeria monocytogenes. In human and murine macrophage-like cell lines, intracellular persistence of these r-BCG strains was reduced as compared to the parental BCG strain. By immunogold labelling Hly was detected in membrane structures and within the phagosomal space of macrophages. Hly fusions consistently co-localized with a lysosome-associated membrane glycoprotein (LAMP-1) suggesting that membrane attack conformation of Hly was not altered. Although r-BCG microorganisms apparently did not egress into the cytoplasmic compartment of host cells, they both improved major histocompatibility complex class I presentation of co-phagocytosed soluble ovalbumin as compared with wild-type BCG microbes. These data suggest that Hly secretion endows BCG with an improved capacity to stimulate CD8 T cells. Because CD8 T cells play a major role in protection against tuberculosis such Hly-secreting r-BCG constructs are anti-tuberculosis vaccine candidates. In addition, we report on our r-Salmonella typhimurium expression system combined with the HlyB/HlyD/ TolC export machinery for delivering the prominent mycobacterial antigen Ag85B for immune recognition.
Keywords: JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL Animal Antigens, Bacterial/GENETICS/IMMUNOLOGY BCG Vaccine/GENETICS/*IMMUNOLOGY Cytotoxins/GENETICS/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Human Salmonella typhimurium/GENETICS Support, Non-U.S. Gov't Tuberculosis/*IMMUNOLOGY/*PREVENTION & CONTROL/THERAPY Vaccines, Synthetic/*IMMUNOLOGY 990730
A9971197
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