title: DNA is an efficient booster of dendritic cell-based vaccine.
abstract: DC-based therapeutic vaccines as a promising strategy against chronic infections and cancer have been validated in several clinical trials. However, DC-based vaccines are complex and require many in vitro manipulations, which makes this a personalized and expensive therapeutic approach. In contrast, DNA-based vaccines have many practical advantages including simplicity, low cost of manufacturing and potent immunogenicity already proven in non-human primates and humans. In this study, we explored whether DC-based vaccines can be simplified by the addition of plasmid DNA as prime or boost to achieve robust CD8-mediated immune responses. We compared the cellular immunity induced in BALB/c and C57BL/6 mice by DC vaccines, loaded either with peptides or optimized SIV Env DNA, and plasmid DNA-based vaccines delivered by electroporation (EP). We found that mature DC loaded with peptides (P-mDC) induced the highest CD8(+) T cell responses in both strains of mice, but those responses were significantly higher in the C57BL/6 model. A heterologous prime-boost strategy (P-DC prime-DNA boost) induced CD8(+) T cell responses similar to those obtained by the P-DC vaccine. Importantly, this strategy elicited robust polyfunctional T cells as well as highest antigen-specific central memory CD8+ T cells in C57BL/6 mice, suggesting long-term memory responses. These results indicate that a DC-based vaccine in combination with DNA in a heterologous DC prime-DNA boost strategy has potential as a repeatedly administered vaccine.
authors.affiliation: a Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute ; Frederick , MD USA.
authors.forename: Jinyao
authors.initials: J
authors.lastname: Li
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.forename: Rachel Kelly
authors.initials: RK
authors.lastname: Beach
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014182:Transplantation, Autologous; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D019444:Vaccines, DNA
keywords: DNA vaccine; dendritic cells; mice; peptide