Vaccination with Irradiated Listeria Induces Protective T Cell Immunity

We evaluated γ-irradiated Listeria monocytogenes as a killed bacterial vaccine, testing the hypothesis that irradiation preserves antigenic and adjuvant structures destroyed by traditional heat or chemical inactivation. Irradiated Listeria monocytogenes (LM), unlike heat-killed LM, efficiently activ...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2006-07, Vol.25 (1), p.143-152
Main Authors: Datta, Sandip K., Okamoto, Sharon, Hayashi, Tomoko, Shin, Samuel S., Mihajlov, Ivan, Fermin, Agnes, Guiney, Donald G., Fierer, Joshua, Raz, Eyal
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation - immunology
Bacteria
Bacterial Proteins - biosynthesis
Cell Differentiation
Cells, Cultured
Cytosol - immunology
Cytosol - metabolism
Dendritic Cells - cytology
Dendritic Cells - metabolism
Flow cytometry
HUMDISEASE
Listeria
Listeria monocytogenes
Listeria monocytogenes - immunology
Listeria monocytogenes - metabolism
Listeria monocytogenes - radiation effects
Listeriosis - immunology
Listeriosis - microbiology
Listeriosis - pathology
Listeriosis - prevention & control
Liver
Lymphocyte Activation - immunology
Lymphocytes
Mice
MICROBIO
Microscopy
MOLIMMUNO
Organisms
Rheumatic diseases
Rodents
Software
Spleen
Studies
Survival Rate
T-Lymphocytes - immunology
Toll-Like Receptors - metabolism
Vaccination
Vaccines
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Summary:We evaluated γ-irradiated Listeria monocytogenes as a killed bacterial vaccine, testing the hypothesis that irradiation preserves antigenic and adjuvant structures destroyed by traditional heat or chemical inactivation. Irradiated Listeria monocytogenes (LM), unlike heat-killed LM, efficiently activated dendritic cells via Toll-like receptors and induced protective T cell responses in mice. Like live LM, irradiated LM induced Toll-like-receptor-independent T cell priming. Cross-presentation of irradiated listerial antigens to CD8 + T cells involved TAP- and proteasome-dependent cytosolic antigen processing. These results establish that killed LM can induce protective T cell responses, previously thought to require live infection. γ-irradiation may be potentially applied to numerous bacterial vaccine candidates, and irradiated bacteria could serve as a vaccine platform for recombinant antigens derived from other pathogens, allergens, or tumors.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2006.05.013