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Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. In the context of DNA vaccines, we previously used the gene gun approach to test several intracellular targeting strategies that are able to route a model antigen, such as(More)
T cell selection and maturation in the thymus depends on the interactions between T cell receptors (TCRs) and different self-peptide-major histocompatibility complex (pMHC) molecules. We show that the affinity of the OT-I TCR for its endogenous positively selecting ligands, Catnb-H-2Kb and Cappa1-H-2Kb, is significantly lower than for previously reported(More)
DNA vaccines have emerged as an attractive approach for antigen-specific cancer immunotherapy. We have previously linked Mycobacterium tuberculosis heat shock protein 70 (HSP70) to human papillomavirus type 16 (HPV-16) E7 in the context of a DNA vaccine. Vaccination with DNA encoding E7/HSP70 has generated a dramatic increase of E7-specific CD8+ T cell(More)
Vaccinia vaccines have become important vectors for antigen-specific immunotherapy. Calreticulin has been shown to enhance MHC class I presentation of linked peptide/protein and may be useful for antigen-specific cancer treatment. An innovative vaccine administering antigen linked to calreticulin via a vaccinia vector may generate a potent antigen-specific(More)
We have recently shown that intradermal coadministration of DNA encoding Ag with DNA encoding inhibitors of apoptosis, including Bcl-x(L), prolongs dendritic cell (DC) life and thereby enhances the potency of DNA vaccines in vivo. We have also demonstrated that DNA vaccines targeting Ag to subcellular compartments, using proteins such as Mycobacterium(More)
DNA-based alphaviral RNA replicon vectors, also called suicidal DNA vectors, alleviate the concerns of integration or transformation related to conventional DNA vectors since suicidal DNA vectors eventually cause apoptosis of transfected cells. However, the expression of inserted genes in these vectors is transient and the potency of suicidal DNA vaccines(More)
Intradermal vaccination with DNA encoding herpes simplex virus type 1 (HSV-1) VP22 linked to antigen leads to spread of antigen within the epithelium and results in enhanced antigen-specific CD8+ T cell immune responses in vaccinated mice. In this study, we characterized the number of antigen-expressing dendritic cells (DCs) in the draining lymph nodes of(More)
Intradermal vaccination by gene gun efficiently delivers DNA vaccines into DCs of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. DCs, however, have a limited life span, hindering their long-term ability to prime antigen-specific T cells. We reason that a strategy that prolongs the survival of DNA-transduced DCs will(More)
One of the major hurdles facing cancer immunotherapy is that cancers may downregulate expression of MHC class I molecules. The development of a suitable tumor model with downregulated MHC class I expression is critical for designing vaccines and immunotherapeutic strategies to control such tumors. We developed an E7-expressing murine tumor model with(More)
It has long been thought that clonal deletion efficiently removes almost all self-specific T cells from the peripheral repertoire. We found that self-peptide MHC-specific CD8(+) T cells in the blood of healthy humans were present in frequencies similar to those specific for non-self antigens. For the Y chromosome-encoded SMCY antigen, self-specific T cells(More)