CCL19 (ELC) as an adjuvant for DNA vaccination: induction of a TH1-type T-cell response and enhancement of antitumor immunity.
Coexpression of tumor antigens together with immunomodulatory molecules is a strategy in DNA vaccination aiming at an amplification of the antitumor immune response. Epstein-Barr virus-induced-molecule-1-ligand-chemokine (ELC/CCL19) is a CC chemokine that binds to the chemokine receptor CCR7. CCR7 is expressed on mature dendritic cells (DC) and distinct T- and B-cell subpopulations. CCL19 (ELC) is mainly expressed in secondary lymphoid organs and plays a central role in regulating the encounters between DC and T cells. We asked whether CCL19 is able to augment immunogenicity of a DNA vaccine in a C57BL/6 mouse model with syngeneic MCA205 (beta-gal) tumor cells. Mice were vaccinated twice intramuscularly on days 1 and 15 and tumor challenge was performed subcutaneously on day 25. Coadministration of plasmid DNA (pDNA) (beta-gal) plus pDNA (CCL19) was compared with pDNA (beta-gal), pDNA (CCL19), mock vector and phosphate-buffered saline (PBS) alone. Coexpression of CCL19 resulted in enhancement of a Th1-polarized immune response with substantial improvement of the protective effect of the DNA vaccine. Immunohistochemical staining revealed an increased CD8+ T-cell infiltration in the tumor tissue of mice that had been immunized with pDNA (beta-gal) plus pDNA (CCL19). We conclude that CCL19 is an attractive adjuvant for DNA vaccination able to augment antitumor immunity and that this effect is partially caused by enhanced CD8+ T-cell recruitment.
Westermann
J
J
Department of Hematology, Charité - University Medicine Berlin, Campus Berlin-Buch, Berlin, Germany. joerg.westermann@charite.de
Nguyen-Hoai
T
T
Baldenhofer
G
G
Höpken
U E
UE
Lipp
M
M
Dörken
B
B
Pezzutto
A
A
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D019742:Chemokines, CC; D019444:Vaccines, DNA