title: Induction of immune responses and safety profiles in rhesus macaques immunized with a DNA vaccine expressing human prostate specific antigen.
abstract: Prostate specific antigen (PSA) is a widely used marker for prostate cancer, which is secreted by normal prostate cells at low levels, but is produced more substantially by cancer cells. We have previously reported on the use of a DNA vaccine construct that encodes for human PSA gene to elicit host immune responses against cells producing PSA. DNA immunization strategy delivers DNA constructs encoding for a specific immunogen into the host, who becomes the in vivo protein source for the production of antigen. This antigen then is the focus of the resulting immune response. In this study, we examine the induction of immune responses and safety profiles in rhesus macaques immunized with DNA-based PSA vaccine. We observed induction of PSA-specific humoral response as well as positive PSA-specific lymphoproliferative (LPA) response in the vaccinated macaques. We also observed that the stimulated T cells from the PSA-immunized rhesus macaques produced higher levels of Th1 type cytokine IFN-gamma than the control vector immunized animals. On the other hand, DNA immunization did not result in any adverse effects in the immunized macaques, as indicated by complete blood counts, leukocyte differentials and hepatic and renal chemistries. The macaques appeared healthy, without any physical signs of toxicity throughout the observation period. In addition, we did not observe any adverse effect on the vaccination site. The apparent safety and immunogenecity of DNA immunization in this study suggest that further evaluation of this vaccination strategy is warranted.
authors.affiliation: Viral Genomix, Inc., Philadelphia, PA 19104, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: J S
authors.initials: JS
authors.lastname: Yang
authors.forename: L K
authors.initials: LK
authors.lastname: Nottingham
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: K
authors.initials: K
authors.lastname: Dang
authors.forename: K H
authors.initials: KH
authors.lastname: Manson
authors.forename: M S
authors.initials: MS
authors.lastname: Wyand
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001772:Blood Cell Count; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D011467:Prostate / Q000187:drug effects; D017430:Prostate-Specific Antigen / Q000276:immunology*; D012449:Safety; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014611:Vaccination / Q000009:adverse effects; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen