DNA vaccination with T-cell epitopes encoded within Ab molecules induces high-avidity anti-tumor CD8+ T cells.
Stimulation of high-avidity CTL responses is essential for effective anti-tumor and anti-viral 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 gamma 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 cross-present 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.
Pudney
Victoria A
VA
Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, City Hospital, Nottingham, UK.
Metheringham
Rachael L
RL
Gunn
Barbara
B
Spendlove
Ian
I
Ramage
Judith M
JM
Durrant
Lindy G
LG
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000915:Antibody Affinity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019444:Vaccines, DNA / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D019444:Vaccines, DNA