Vaccination with irradiated Listeria induces protective T cell immunity

被引:79
作者
Datta, Sandip K.
Okamoto, Sharon
Hayashi, Tomoko
Shin, Samuel S.
Mihajlov, Ivan
Fermin, Agnes
Guiney, Donald G.
Fierer, Joshua
Raz, Eyal
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[2] San Diego Vet Affairs Med Ctr, Dept Med, San Diego, CA 92161 USA
关键词
D O I
10.1016/j.immuni.2006.05.013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 (I-M), 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.
引用
收藏
页码:143 / 152
页数:10
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