Adjuvant properties of listeriolysin O protein in a DNA vaccination strategy.
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-1alpha 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.
Peng
Xiaohui
X
Department of Microbiology, University of Pennsylvania School of Medicine, 323 Johnson Pavilion, 36th St. and Hamilton Walk, Philadelphia, PA 19104-6076, USA.
Treml
John
J
Paterson
Yvonne
Y
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology / Q000627:therapeutic use*; D006460:Hemolysin Proteins / Q000276:immunology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D019496:Cancer Vaccines; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D019402:Macrophage Inflammatory Proteins; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C038705:hlyA protein, Listeria monocytogenes