SAFETY/IMMUNE RESPONSE TO DNA PLASMID VACCINE IN ASYMPTOMATIC HIV

我们已经证明，DNA质粒构建物可以驱动 非人灵长类动物中的HIV-1基因，同时诱导细胞和体液 免疫反应。我们现在报告15名艾滋病毒感染者，因为 疫苗在剂量范围内的研究(30、100和300ag)。研究对象： CD4细胞计数=500在10周内接受3次肌肉注射疫苗 每隔一段时间进行36周的随访。截至96年10月1日，所有3剂 队列已经接种了全部3剂，其中9人最近接种了+4 几个月的助推剂，都没有局部或系统临床的证据 毒性。血细胞计数、尿检、血肌酐、醛缩酶或 肝脏的化学成分发生了变化；肌酸激酶的三次短暂上升 发生了。无一例出现抗核或抗DNA抗体。CD_4计数 2个月上涨20%，4个月下降；3个月CD8增长20%，3个月下降 4.病毒载量在1个月内增加了0.5个对数，在1个月内下降了0.5个。 与剂量相关的抗env抗体升高，也与时间相关。 CTL对表达env的靶细胞的应答。参数包括 细胞因子分析正在研究中。疫苗似乎是安全有效的 诱导对艾滋病毒抗原的特异性免疫反应。

We have shown that a DNA plasmid construct can drive expression of HIV-1 genes in non-human primates, inducing both cellular and humoral immune responses. We now report 15 HIV-infected subjects given the vaccine in a dose-ranging study (30, 100, and 300aeg). Subjects with CD4 cell counts >=500 received 3 intramuscular vaccine doses at 10 week intervals with follow-up for 36 weeks. As of 10/1/96, all 3 dose cohorts have received all 3 doses, and 9 have recently received a +4 months booster, all without evidence of local or systemic clinical toxicity. Neither have CBC, urinalysis, serum creatinine, aldolase, or liver chemistries changed; 3 transient rises in creatine kinase have occurred. None developed antinuclear or antiDNA antibodies. CD4 counts rose >=20% in 2, and fell in 4; CD8 increased >=20% in 3, and fell in 4. Viral load increased by >=0.5 log in 1, and fell by >=0.5 in 1. Dose-related rises in anti-env antibody occurred, as did time-dependent CTL responses to env-expressing target cells. Parameters including cytokine analysis are under study. The vaccine appears safe and capable of inducing specific immune responses to HIV antigens.