CpG motifs are efficient adjuvants for DNA cancer vaccines.
DNA vaccines can induce impressive specific cellular immune response (IR) when taking advantage of their recognition as pathogen-associated molecular patterns (PAMP) through Toll-like receptors (TLR) expressed on/in cells of the innate immune system. Among the many types of PAMP, immunostimulatory DNA, so-called CpG motifs, was shown to interact specifically with TLR9, which is expressed in plasmacytoid dendritic cells (pDC), a key regulatory cell for the activation of innate and adaptive IR. We now report that CpG motifs, when introduced into the backbone, are a useful adjuvant for plasmid-based DNA (pDNA) vaccines to induce melanoma antigen-specific protective T cell responses in the Cloudman M3/DBA/2 model. The CpG-enriched pDNA vaccine induced protection against subsequent challenge with melanoma cells at significantly higher levels than its parental unmodified vector. Preferential induction of an antigen-specific, protective T cell response could be demonstrated by (i) induction of antigen-dependent tumor cell protection, (ii) complete loss of protection by in vivo CD4+/CD8+T cell- but not NK cell-depletion, and (iii) the detection of antigen-specific T cell responses but not of relevant NK cell activity in vitro. These results demonstrate that employing PAMP in pDNA vaccines improves the induction of protective, antigen-specific, T cell-mediated IR.
Schneeberger
Achim
A
Division of Immnunology, Allergy, and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Wagner
Christine
C
Zemann
Anja
A
Lührs
Petra
P
Kutil
Raphaela
R
Goos
Manfred
M
Stingl
Georg
G
Wagner
Stephan N
SN
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D000939:Epitopes; D005260:Female; D005822:Genetic Vectors; D008545:Melanoma / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008811:Mice, Inbred DBA; D010957:Plasmids; D012878:Skin Neoplasms / Q000276:immunology / Q000517:prevention & control*; D019076:Transgenes / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D000939:Epitopes; D019444:Vaccines, DNA