Swain W E, Heydenburg Fuller D, Wu M S, Barr L J, Fuller J T, Culp J, Burkholder J, Dixon R M, Widera G, Vessey R, Roy M J
PowderJect Vaccines, Inc., Madison, WI 53711, USA.
Dev Biol (Basel). 2000;104:115-9.
We are developing a DNA vaccine toward hepatitis-B virus (HBV) using PowderJect's proprietary needle-free technology to deliver DNA-coated gold particles directly into cells of the skin. Preclinical studies in animals showed that (i) microgram doses of the DNA vaccine were sufficient to immunize pigs and non-human primates to antibody levels comparable to those obtained with a commercial recombinant subunit vaccine; (ii) the DNA vaccine was effective in mouse strains that respond poorly to protein subunit vaccines; (iii) the vaccine induces robust cytotoxic T-cell responses, and (iv) the vaccine is non-toxic and well tolerated. Based on these findings, this DNA vaccine was evaluated for safety, tolerability, and the induction of immune responses in phase 1 clinical studies in healthy, hepatitis-naïve human volunteers. Preliminary results indicate that the vaccine is safe and well tolerated, and elicits both humoral and cellular immune responses in man.
我们正在利用PowderJect公司的专利无针技术研发一种针对乙型肝炎病毒（HBV）的DNA疫苗，该技术可将包裹DNA的金颗粒直接递送至皮肤细胞。动物临床前研究表明：（i）微克剂量的DNA疫苗足以使猪和非人类灵长类动物产生抗体水平，与使用商业重组亚单位疫苗所获得的抗体水平相当；（ii）DNA疫苗对蛋白亚单位疫苗反应不佳的小鼠品系有效；（iii）该疫苗可诱导强烈的细胞毒性T细胞反应；（iv）该疫苗无毒且耐受性良好。基于这些发现，在健康、未感染过肝炎的人类志愿者中进行了1期临床研究，对这种DNA疫苗的安全性、耐受性和免疫反应诱导情况进行了评估。初步结果表明，该疫苗安全且耐受性良好，并在人体中引发了体液免疫和细胞免疫反应。
