Design of immunogenic and effective multi-epitope DNA vaccines for melanoma |
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Authors: | Hyun-Il Cho Esteban Celis |
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Institution: | (1) Cancer Vaccine Group, Immunology Program, Moffitt Cancer Center, 12902 Magnolia Drive, SRB2, Tampa, FL 33612, USA;(2) Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA; |
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Abstract: | Plasmid DNA vaccination is an attractive way to elicit T cell responses against infectious agents and tumor cells. DNA constructs
can be designed to contain multiple T cell epitopes to generate a diverse immune response to incorporate numerous antigens
and to reduce limitations due to MHC restriction into a single entity. We have prepared cDNA plasmid constructs containing
several mouse T cell epitopes connected by either furin-sensitive or furin-resistant linkers and studied the effects of a
cationic cell-penetrating sequence from HIV-tat. Significant CD8 T cell responses were obtained with multi-epitope DNA vaccines
followed by in vivo electroporation regardless of the type of linker used and whether the construct had the HIV-tat sequence.
The magnitude of immune responses was very similar to all CD8 T cell epitopes contained within each vaccine construct, indicating
the absence of immunodominance. Incorporating a T helper epitope into the constructs increased the T cell responses. Prophylactic
and therapeutic antitumor responses against B16 melanoma were obtained using a construct containing epitopes from melanosomal
proteins, indicating that this vaccination was successful in generating responses to self-antigens that potentially may be
subjected to immune tolerance. These findings are useful for designing DNA vaccines for a multitude of diseases where T lymphocytes
play a protective or therapeutic role. |
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