Cancer Immunology, Immunotherapy

, Volume 56, Issue 6, pp 885–895

Plasmid DNA vaccine encoding prostatic acid phosphatase is effective in eliciting autologous antigen-specific CD8+ T cells

  • Laura E. Johnson
  • Thomas P. Frye
  • Nachimuthu Chinnasamy
  • Dhanalakshmi Chinnasamy
  • Douglas G. McNeel
Original Article


Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and a prostate-specific protein shared by rats and humans. Previous studies indicated that Copenhagen rats immunized with a recombinant vaccinia virus expressing human PAP (hPAP) developed PAP-specific cytotoxic T cells (CTL) with cross reactivity to rat PAP (rPAP) and evidence of prostate inflammation. Viral delivery of vaccine antigens is an active area of clinical investigation. However, a potential difficulty with viral-based immunizations is that immune responses elicited to the viral vector might limit the possibility of multiple immunizations. In this paper, we investigate the ability of another genetic immunization method, a DNA vaccine encoding PAP, to elicit antigen-specific CD8+ T cell immune responses. Specifically, Lewis rats were immunized with either a plasmid DNA-based (pTVG-HP) or vaccinia-based (VV-HP) vaccine each encoding hPAP. We determined that rats immunized with a DNA vaccine encoding hPAP developed a Th1-biased immune response as indicated by proliferating PAP-specific CD4+ and CD8+ cells and IFNγ production. Rats immunized with vaccinia virus encoding PAP did not develop a PAP-specific response unless boosted with a heterologous vaccination scheme. Most importantly, multiple immunizations with a DNA vaccine encoding the rat PAP homologue (pTVG-RP) could overcome peripheral self-tolerance against rPAP and generate a Th1-biased antigen-specific CD4+ and CD8+ T cell response. Overall, DNA vaccines provide a safe and effective method of generating prostate antigen-specific T cell responses. These findings support the investigation of PAP-specific DNA vaccines in human clinical trials.


Prostatic acid phosphatase DNA vaccine Prostate cancer Rat 





Bovine serum albumin


Complete Freund’s adjuvant


Cytotoxic T lymphocytes


Dendritic cell


Ethylenediaminetetraacetic acid


Enzyme-linked immunosorbent assay


Green fluorescent protein


Granulocyte macrophage colony-stimulating factor


Human prostatic acid phosphatase


Incomplete Freund’s adjuvant




Immunoglobulin G




Major histocompatibility complex


Multiplicity of infection


Optical density


Prostatic acid phosphatase


Phosphate buffered saline


Plaque-forming unit




DNA vaccine encoding hPAP


DNA vaccine encoding rPAP


Rat prostatic acid phosphatase


Standard error




Recombinant vaccinia virus encoding hPAP


Wild type vaccinia virus


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Laura E. Johnson
    • 1
  • Thomas P. Frye
    • 1
  • Nachimuthu Chinnasamy
    • 2
  • Dhanalakshmi Chinnasamy
    • 2
  • Douglas G. McNeel
    • 1
    • 3
  1. 1.Department of MedicineUniversity of WisconsinMadisonUSA
  2. 2.Vince Lombardi Gene Therapy Laboratory, Immunotherapy ProgramSt. Luke’s Medical CenterMilwaukeeUSA
  3. 3.K4/518 Clinical Science CenterMadisonUSA

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