SAFETY/IMMUNE RESPONSE TO DNA PLASMID VACCINE IN ASYMPTOMATIC HIV

无症状 HIV 患者对 DNA 质粒疫苗的安全性/免疫反应

• 批准号: 6274471
• 负责人: ROB R MACGREGOR
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-15 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6274471
• 关键词: AIDS therapy; AIDS vaccines; HIV infections; T lymphocyte; antigen antibody reaction; cellular immunity; clinical research; clinical trial phase I; drug screening /evaluation; human subject; human therapy evaluation; immunity; outcomes research; pathologic process; vector vaccine

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.

我们已经证明，DNA质粒构建体可以驱动 HIV-1基因在非人灵长类动物中，诱导细胞和体液免疫 免疫反应。 我们现在报告15名艾滋病毒感染者， 疫苗剂量范围研究（30、100和300 aeg）。 受试者 CD 4细胞计数>=500，在第10周接受3次肌内接种疫苗 随访36周。 截至1996年10月1日，所有3剂 队列接受了所有3剂，9个队列最近接受了+4剂 个月的加强剂，均无局部或全身临床 毒性 CBC、尿分析、血清肌酐、醛缩酶或 肝脏化学改变; 3例肌酸激酶一过性升高， 发生了。 没有人产生抗核抗体或抗DNA抗体。 cd 4计数 2例升高>=20%，4例下降; 3例CD 8升高>=20%， 4. 病毒载量增加>=0.5 log/1，下降>=0.5 log/1。 抗env抗体的升高与剂量有关，与时间有关 对env表达靶细胞的CTL应答。 参数包括 细胞因子分析正在研究中。 疫苗看起来是安全的， 诱导对HIV抗原的特异性免疫反应。