Abstract
There are few vaccination strategies available for the reproducible generation of a cytotoxic T cell (CTL) response, particularly in the setting of immunizing against a tumor antigen. Plasmid-based DNA vaccination offers several advantages as compared to MHC class I peptide-based vaccines or DNA immunization using viral vectors. Plasmid-based DNA vaccines are easily produced, can potentially elicit both an MHC class I and class II response, and have little infectious potential. Plasmid-based vaccines, however, have been poorly immunogenic. The systemic immune response generated after plasmid vaccination relies on in vivo transfection of local antigen presenting cells (APC) and both direct presentation and "cross priming" of antigen by professional and non-professional APC. Therefore, methods to enhance the function of APC, such as simultaneous inoculation with plasmids encoding cytokine genes, has resulted in an enhancement of detectable immunity after vaccination. We questioned whether local application of soluble cytokines would be effective in enhancing the systemic immune response elicited after DNA vaccination. Using a self-tumor antigen model, we vaccinated rats with a plasmid-based rat neu intracellular domain (ICD) DNA construct and either no adjuvant, soluble GM-CSF, or IL-12. We demonstrate that the addition of soluble GM-CSF or IL-12 to rat neu ICD DNA vaccination elicits detectable neu specific T cell immunity; specifically the generation of CTL. Antibodies directed against rat neu were not elicited with this approach, indicating that the neu specific T cell immune response elicited with plasmid DNA was skewed towards cell-mediated rather than humoral immunity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 179-186 |
| Number of pages | 8 |
| Journal | Immunobiology |
| Volume | 207 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Soluble cytokines can act as effective adjuvants in plasmid DNA vaccines targeting self tumor antigens. / Disis, Mary L.; Shiota, Faith M.; McNeel, Douglas G.; Knutson, Keith L.
In: Immunobiology, Vol. 207, No. 3, 2003, p. 179-186.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Soluble cytokines can act as effective adjuvants in plasmid DNA vaccines targeting self tumor antigens
AU - Disis, Mary L.
AU - Shiota, Faith M.
AU - McNeel, Douglas G.
AU - Knutson, Keith L
PY - 2003
Y1 - 2003
N2 - There are few vaccination strategies available for the reproducible generation of a cytotoxic T cell (CTL) response, particularly in the setting of immunizing against a tumor antigen. Plasmid-based DNA vaccination offers several advantages as compared to MHC class I peptide-based vaccines or DNA immunization using viral vectors. Plasmid-based DNA vaccines are easily produced, can potentially elicit both an MHC class I and class II response, and have little infectious potential. Plasmid-based vaccines, however, have been poorly immunogenic. The systemic immune response generated after plasmid vaccination relies on in vivo transfection of local antigen presenting cells (APC) and both direct presentation and "cross priming" of antigen by professional and non-professional APC. Therefore, methods to enhance the function of APC, such as simultaneous inoculation with plasmids encoding cytokine genes, has resulted in an enhancement of detectable immunity after vaccination. We questioned whether local application of soluble cytokines would be effective in enhancing the systemic immune response elicited after DNA vaccination. Using a self-tumor antigen model, we vaccinated rats with a plasmid-based rat neu intracellular domain (ICD) DNA construct and either no adjuvant, soluble GM-CSF, or IL-12. We demonstrate that the addition of soluble GM-CSF or IL-12 to rat neu ICD DNA vaccination elicits detectable neu specific T cell immunity; specifically the generation of CTL. Antibodies directed against rat neu were not elicited with this approach, indicating that the neu specific T cell immune response elicited with plasmid DNA was skewed towards cell-mediated rather than humoral immunity.
AB - There are few vaccination strategies available for the reproducible generation of a cytotoxic T cell (CTL) response, particularly in the setting of immunizing against a tumor antigen. Plasmid-based DNA vaccination offers several advantages as compared to MHC class I peptide-based vaccines or DNA immunization using viral vectors. Plasmid-based DNA vaccines are easily produced, can potentially elicit both an MHC class I and class II response, and have little infectious potential. Plasmid-based vaccines, however, have been poorly immunogenic. The systemic immune response generated after plasmid vaccination relies on in vivo transfection of local antigen presenting cells (APC) and both direct presentation and "cross priming" of antigen by professional and non-professional APC. Therefore, methods to enhance the function of APC, such as simultaneous inoculation with plasmids encoding cytokine genes, has resulted in an enhancement of detectable immunity after vaccination. We questioned whether local application of soluble cytokines would be effective in enhancing the systemic immune response elicited after DNA vaccination. Using a self-tumor antigen model, we vaccinated rats with a plasmid-based rat neu intracellular domain (ICD) DNA construct and either no adjuvant, soluble GM-CSF, or IL-12. We demonstrate that the addition of soluble GM-CSF or IL-12 to rat neu ICD DNA vaccination elicits detectable neu specific T cell immunity; specifically the generation of CTL. Antibodies directed against rat neu were not elicited with this approach, indicating that the neu specific T cell immune response elicited with plasmid DNA was skewed towards cell-mediated rather than humoral immunity.
UR - http://www.scopus.com/inward/record.url?scp=0038528567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038528567&partnerID=8YFLogxK
U2 - 10.1078/0171-2985-00230
DO - 10.1078/0171-2985-00230
M3 - Article
C2 - 12777059
AN - SCOPUS:0038528567
VL - 207
SP - 179
EP - 186
JO - Immunobiology
JF - Immunobiology
SN - 0171-2985
IS - 3
ER -