DNA vaccination with T-cell epitopes encoded within Ab molecules induces high-avidity anti-tumor CD8+ T cells

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Abstract

Stimulation of high-avidity CTL responses is essential for effective anti-tumor and antiviral vaccines. In this study we have demonstrated that a DNA vaccine incorporating CTL epitopes within an Ab molecule results in high-avidity T-cell responses to both foreign and self epitopes. The avidity and frequency was superior to peptide, peptide-pulsed DC vaccines or a DNA vaccine incorporating the epitope within the native Ag. The DNA Ab vaccine was superior to an identical protein vaccine that can only cross-present, indicating a role for direct presentation by the DNA vaccine. However, the avidity of CTL responses was significantly reduced in Fc receptor c knockout mice or if the Fc region was removed suggesting that cross presentation of Ag via Fc receptor was also important in the induction of high-avidity CTL. These results suggest that generation of high-avidity CTL responses by the DNA vaccine is related to its ability to both directly present and crosspresent the epitope. High-avidity responses were capable of efficient anti-tumor activity in vitro and in vivo. This study demonstrates a vaccine strategy to generate high-avidity CTL responses that can be used in anti-tumor and anti-viral vaccine settings. & 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

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Pudney, V. A., Metheringham, R. L., Gunn, B., Spendlove, I., Ramage, J. M., & Durrant, L. G. (2010). DNA vaccination with T-cell epitopes encoded within Ab molecules induces high-avidity anti-tumor CD8+ T cells. European Journal of Immunology, 40(3), 899–910. https://doi.org/10.1002/eji.200939857

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