First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: Safety and host response

First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: Safety and host response
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DOI:
10.1086/515613
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发表时间:
1998-07-01
影响因子:
6.4
通讯作者:
Weiner, DB
Weiner, DB
中科院分区:
医学2区
文献类型:
--
作者:
MacGregor, RR;Boyer, JD;Weiner, DB

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在15名未使用抗病毒药物且CD4(+)淋巴细胞计数大于或等于每微升血液500的无症状hiv感染患者中,研究了一种含有人类免疫缺陷病毒1型(HIV-1) env和rev基因的基于dna的疫苗的安全性和宿主免疫反应。在剂量递增试验中,连续组每隔10周接种三剂疫苗(30,100或300 μ g)。接种疫苗未引起局部或全身反应,也未发现实验室异常。具体来说,没有患者出现抗dna抗体或肌肉酶升高。CD4或CD8淋巴细胞计数或血浆HIV浓度未发生一致的变化。在100和300 μ g组中,个别患者的gp120抗体增加。细胞毒性T淋巴细胞对gp160靶细胞的活性和淋巴细胞增殖活性均有所增加。一种hiv定向dna疫苗的安全性和潜在的免疫原性已得到证实,这一发现应鼓励进一步的研究。
A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env and rev genes was tested for safety and host immune response In 15 asymptomatic HIV-infected patients who were not using antiviral drugs and who had CD4(+) lymphocyte counts of greater than or equal to 500 per microliter of blood. Successive groups received three doses of vaccine (30, 100, or 300 mu g) at 10-week intervals in a dose-escalation trial. Vaccine administration induced no local or systemic reactions, and no laboratory abnormalities were detected. Specifically, no patient developed anti-DNA antibody or muscle enzyme elevations. No consistent change occurred in CD4 or CD8 lymphocyte counts or in plasma HIV concentration. Antibody against gp120 increased in individual patients in the 100- and 300-mu g groups. Some increases were noted in cytotoxic T lymphocyte activity against gp160-bearing targets and in lymphocyte proliferative activity. The safety and potential immunogenicity of an HIV-directed DNA-based vaccine was demonstrated, a finding that should encourage further studies.