Augmenting the immunogenicity of DNA vaccines: role of plasmid-encoded Flt-3 ligand, as a molecular adjuvant in genetic vaccination.
In this study, we have taken advantage of the unique property of a potent dendritic cell (DC) growth factor, Flt-3 ligand (FL), which could act as a vaccine adjuvant. Accordingly, a single injection of plasmid DNA coding for soluble FL (FLex) was shown to induce large numbers of DCs in various tissue compartments and was critical for generating high frequencies of antigen-specific (HIV gp120 and LCMV NP) immune responses in mice. Interestingly, this enhanced level of immune response is strictly dependent on the co-delivery (i.m.) of the DNA vaccines and hFLex DNA to mice harboring large numbers of DCs. The high frequencies of antigen-specific CD8(+) T cells were largely associated with the expansion phase of DCs in vivo. However, DC expansion and immune enhancement have not reciprocally maintained a linear correlation, suggesting that other factors, cytokines/chemokines, which have the potential to modulate the microenvironment of DCs, could influence immunological outcome in this vaccination modality.
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA.
Bishnu P
BP
Nayak
Gangadhara
G
Sailaja
Abdul M
AM
Jabbar
D000276:Adjuvants, Immunologic / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D008565:Membrane Proteins; D009698:Nucleoproteins; D019444:Vaccines, DNA; D014764:Viral Proteins; C084881:flt3 ligand protein