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Influence of virulence attenuation on the efficacy of Listeria monocytogenes as a vaccine vector for stimulating anti‐tumor immunity
Author(s) -
Smithey Megan J,
Higgins Darren,
Freitag Nancy E,
Bouwer H.G. Archie
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1077.12
Subject(s) - cd8 , adjuvant , immunity , vaccination , listeria monocytogenes , biology , immunology , immune system , t cell , immunotherapy , mhc class i , cancer research , genetics , bacteria
Listeria monocytogenes (Lm) has been extensively studied as a paradigm for stimulating cell mediated immunity. Its’ cytosolic replication niche allows secreted proteins to access the MHC class I pathway, such that Lm infection generates long‐lived memory CD8 T cells. Because of its’ potent adjuvant properties and efficacy at stimulating T‐cell responses, Lm is being studied as a vaccine platform for stimulating anti‐tumor immunity. In this study we compared the therapeutic efficacy of wildtype (WT) and virulence attenuated recombinant Lm strains in stimulating tumor specific CD8 T cells in melanoma‐bearing mice. We evaluated the functional and phenotypic properties of vaccine‐elicited CD8 T cells and assessed the ability of these cells to control the growth of both lung metastases and subcutaneous solid tumors. Although assays of CD8 T‐cell effector function revealed comparable stimulation by wildtype vs. attenuated Lm strains, attenuation decreased the ability of the anti‐tumor CD8 T cells to control the outgrowth of subcutaneous solid tumors, with less impact on the control of lung tumor growth. This may reflect a differential effect on regulatory T cells, as only vaccination with WT Lm decreased the Treg frequency at the tumor site. If attenuated vectors are to be pursued, a better understanding of how attenuation influences vaccine efficacy is necessary. This work was supported by VA Merit Review and NIH funds.