Enhancement of DNA Vaccine Potency by Linkage of Antigen Gene to the Extracellular Domain of FLT3-Ligand Gene

professional antigen presenting cells (APCs), particularly dendritic cells (DCs). A recombinant chimera of the extracellular domain of Flt3-ligand (FL) linked to a model antigen may potentially target the antigen to DCs and their precursor cells. Using HPV-16 E7 as a model antigen, we evaluated the effect of linkage to the FL on the potency of antigen-specific immunity generated by naked DNA vaccines administered intradermally via gene gun. We found that vaccines containing chimeric FL-E7 fusion genes dramatically increased the frequency of E7-specific CD8+ T cells relative to vaccines containing the wild-type E7 gene. In vitro studies indicated that cells transfected with FL-E7 DNA presented E7 antigen through the MHC class I pathway more efficiently than wild-type E7 DNA. Furthermore, bone marrow-derived DCs pulsed with cell lysates containing FL-E7 fusion protein presented E7 antigen through the MHC class I pathway more efficiently than DCs pulsed with cell lysates containing wild-type E7 protein. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The FL-E7 fusion vaccines mainly targeted CD8+ T cells and anti-tumor effects were completely CD4-independent. These results indicate that fusion of a gene encoding the extracellular domain of Flt3-ligand to an antigen gene may greatly enhance the potency of DNA vaccines via CD8-dependent pathways. Description (Set) Proposed Use (Set) The technology may be used for the development of preventive and therapeutic vaccines for infectious diseases and cancers in human and animals

Inventor(s): Wu, T.C.

Type of Offer: Licensing



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