CCL19 as an adjuvant for intradermal gene gun immunization in a Her2eu mouse tumor model: improved vaccine efficacy and a role for B cells as APC

摘要

The aim of this study was to evaluate the efficacy of the chemokine CCL19 (ELC) as an adjuvant for intradermal gene gun delivery of Her2eu DNA and to investigate the role of B cells in CCL19-mediated enhancement of immune responses. Balb/c mice were immunized intramuscularly (i.m.) on days 1 and 15 with plasmid DNA (pDNA) (100?μg DNA) or intradermally (i.d.) by gene gun delivery (1–2?μg DNA). Administration of pDNA encoding Her2eu (pDNA(Her2eu) was compared with pDNA(Her2eu) plus pDNA(CCL19), pDNA(CCL19), mock vector or uncoated gold particles/phosphate-buffered saline (PBS). Tumor challenge was performed subcutaneously on day 25 with syngeneic Her2eu+ tumor cells (D2F2/E2). Intradermal immunization by gene gun led to an enhancement of tumor protection by the DNA vaccine as compared with i.m. immunization. The protective effect of the vaccine was further enhanced by coadministration of pDNA(CCL19) both after i.m. and i.d. immunization. Tumor protection was associated with Her2eu-specific T cell and humoral immune responses. Experiments in B-cell-deficient μMT mice showed that B cells are crucial for CCL19-mediated enhancement of tumor rejection, most likely as antigen-presenting B cells. DNA vaccines against Her2eu may play a future role in the treatment of Her2eu-positive breast cancer patients in a clinical situation of minimal residual disease.