TY - JOUR
T1 - Listeriolysin O-deficient Listeria monocytogenes as a vaccine delivery vehicle
T2 - Antigen-specific CD8 T cell priming and protective immunity
AU - Hamilton, Sara E.
AU - Badovinac, Vladimir P.
AU - Khanolkar, Aaruni
AU - Harty, John T.
PY - 2006/9/15
Y1 - 2006/9/15
N2 - Strains of Listeria monocytogenes (LM) that are deficient in the virulence factor listeriolysin O (LLO) are highly attenuated and are thought not to elicit protective immunity. TMs failure has been attributed to the inability of the bacterium to enter the host cell cytosol and access MHC class I Ag processing machinery. We reexamined this issue using recombinant strains of. LM that are deficient in LLO but express an additional CD8 T cell epitope derived from lymphocytic choriomeningitis virus. After infection with LLO-deficient strains, we find sizable priming of epitope-specific CD8 T cells and the development of a functional memory cell population. Mice primed with the LLO-deficient LM strain are equally resistant against high-dose challenge with virulent LM as mice primed with wild-type virulent bacteria and also resist heterologous challenge with lymphocytic choriomeningitis virus. Interestingly, priming with a low dose of LLO-deficient LM, which occurred in environment of reduced inlammation (IFN-γ), allowed rapid amplification of Ag-specific CD8 T cells by booster immunization, despite an undetectable primary response. We conclude that the generation of protective immunity by LLO-deficient strains of LM does in fact occur and that this highly attenuated LM strain may be a useful platform for vaccine delivery.
AB - Strains of Listeria monocytogenes (LM) that are deficient in the virulence factor listeriolysin O (LLO) are highly attenuated and are thought not to elicit protective immunity. TMs failure has been attributed to the inability of the bacterium to enter the host cell cytosol and access MHC class I Ag processing machinery. We reexamined this issue using recombinant strains of. LM that are deficient in LLO but express an additional CD8 T cell epitope derived from lymphocytic choriomeningitis virus. After infection with LLO-deficient strains, we find sizable priming of epitope-specific CD8 T cells and the development of a functional memory cell population. Mice primed with the LLO-deficient LM strain are equally resistant against high-dose challenge with virulent LM as mice primed with wild-type virulent bacteria and also resist heterologous challenge with lymphocytic choriomeningitis virus. Interestingly, priming with a low dose of LLO-deficient LM, which occurred in environment of reduced inlammation (IFN-γ), allowed rapid amplification of Ag-specific CD8 T cells by booster immunization, despite an undetectable primary response. We conclude that the generation of protective immunity by LLO-deficient strains of LM does in fact occur and that this highly attenuated LM strain may be a useful platform for vaccine delivery.
UR - http://www.scopus.com/inward/record.url?scp=33748485157&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748485157&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.6.4012
DO - 10.4049/jimmunol.177.6.4012
M3 - Article
C2 - 16951364
AN - SCOPUS:33748485157
SN - 0022-1767
VL - 177
SP - 4012
EP - 4020
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -