Vaccination with irradiated Listeria induces protective T cell immunity.
We evaluated gamma-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. gamma-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.
Datta
Sandip K
SK
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, 92093, USA. sdatta@ucsd.edu
Okamoto
Sharon
S
Hayashi
Tomoko
T
Shin
Samuel S
SS
Mihajlov
Ivan
I
Fermin
Agnes
A
Guiney
Donald G
DG
Fierer
Joshua
J
Raz
Eyal
E
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001426:Bacterial Proteins / Q000096:biosynthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism; D014611:Vaccination
D001426:Bacterial Proteins; D051193:Toll-Like Receptors