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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Acknowledgments
We dedicate this work to the memory of our friend and colleague Dr. Joseph Lustgarten, tumor immunologist who passed away on June 30, 2011. This work was supported by a grant from the Moffitt Comprehensive Melanoma Research Center. The authors declare no conflict of interest.
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Cho, HI., Celis, E. Design of immunogenic and effective multi-epitope DNA vaccines for melanoma. Cancer Immunol Immunother 61, 343–351 (2012). https://doi.org/10.1007/s00262-011-1110-7
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DOI: https://doi.org/10.1007/s00262-011-1110-7