Kim J J, Yang J S, Nottingham L K, Tang W, Dang K, Manson K H, Wyand M S, Wilson D M, Weiner D B
Viral Genomix, Inc., Philadelphia, PA 19104, USA.
Oncogene. 2001 Jul 27;20(33):4497-506. doi: 10.1038/sj.onc.1204542.
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.
前列腺特异性抗原(PSA)是一种广泛应用于前列腺癌的标志物,正常前列腺细胞会少量分泌该物质,但癌细胞分泌量更多。我们之前曾报道过使用一种编码人PSA基因的DNA疫苗构建体来引发宿主针对产生PSA细胞的免疫反应。DNA免疫策略将编码特定免疫原的DNA构建体递送至宿主体内,宿主成为产生抗原的体内蛋白质来源。然后,这种抗原就成为后续免疫反应的焦点。在本研究中,我们检测了用基于DNA的PSA疫苗免疫恒河猴后免疫反应的诱导情况和安全性。我们观察到接种疫苗的恒河猴体内诱导出了PSA特异性体液反应以及阳性的PSA特异性淋巴细胞增殖(LPA)反应。我们还观察到,与对照载体免疫的动物相比,来自PSA免疫的恒河猴的受刺激T细胞产生了更高水平的Th1型细胞因子干扰素-γ。另一方面,全血细胞计数、白细胞分类以及肝脏和肾脏生化指标显示,DNA免疫在免疫的恒河猴中未产生任何不良反应 在整个观察期内,恒河猴看起来健康,没有任何毒性的体征。此外,我们未观察到疫苗接种部位有任何不良反应。本研究中DNA免疫明显的安全性和免疫原性表明,有必要对这种疫苗接种策略进行进一步评估。