Abstract
The use of infectious agents as vaccine adjuvants has shown utility in both prophylactic and therapeutic vaccinations. Listeria monocytogenes has been used extensively as a vaccine vehicle due to its ability to initiate both CD4+ and CD8+ immune responses. Previous work from this laboratory has used transgenic Listeria to deliver vaccine constructs. A chimeric protein composed of tumor antigen and a non-hemolytic variant of the Listeria protein, listeriolysin O (LLO), has demonstrated effective tumor protection beyond that of antigen alone expressed in the same system. To address the question of how fusion with LLO improves vaccine efficacy, we constructed a number of DNA plasmid vaccines to isolate this effect in the absence of other endogenous Listeria effects. Here we have analyzed the ability of these vaccines to induce the regression of previously established tumors. A vaccine strategy using DNA vaccines bearing the tumor antigen either alone or in combination with LLO in addition to plasmids encoding MIP-1α and GM-CSF was examined. Further, LLO was used either as a chimera or in a bicistronic construct to address the importance of fusion between these elements. Notably, the strategies employing both chimeric and bicistronic vaccines were effective in reducing tumor burden suggesting that LLO can act as an adjuvant that does not require fusion with the tumor antigen to mediate its effect.
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Abbreviations
- LLO:
-
Listeriolysin O
- GM-CSF:
-
Granulocytes macrophage-colony stimulating factor
- MIP-1α:
-
Macrophage inflammatory protein-1α
- DC:
-
Dendritic cells
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Acknowledgments
This work was supported by grant number CA69632 from the National Institute of Health and American Cancer Society grant number TURSG LIB-01-168-01. Yvonne Paterson wishes to disclose that she has a financial interest in Advaxis Inc., a vaccine and therapeutic company that has licensed or has an option to license all patents from the University of Pennsylvania that concern the use of Listeria or listerial products as vaccines.
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Peng, X., Treml, J. & Paterson, Y. Adjuvant properties of listeriolysin O protein in a DNA vaccination strategy. Cancer Immunol Immunother 56, 797–806 (2007). https://doi.org/10.1007/s00262-006-0240-9
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DOI: https://doi.org/10.1007/s00262-006-0240-9