Open AccessLive antigen carriers as tools for improved anti‐tuberculosis vaccines 1
Author(s) -
Hess Jürgen,
Kaufmann Stefan H.E
Publication year - 1999
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.1999.tb01236.x
Subject(s) - biology , microbiology and biotechnology , antigen , mycobacterium tuberculosis , antigen presentation , listeriolysin o , secretion , immune system , listeria monocytogenes , intracellular parasite , mycobacterium bovis , major histocompatibility complex , cd8 , virology , t cell , tuberculosis , immunology , listeria , bacteria , biochemistry , medicine , genetics , pathology
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.