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.