Phase I Study of a Herpes Simplex Virus Type 2 (HSV-2) DNA Vaccine Administered to Healthy, HSV-2-Seronegative Adults by a Needle-Free Injection System
Phase I Study of a Herpes Simplex Virus Type 2 (HSV-2) DNA Vaccine Administered to Healthy, HSV-2-Seronegative Adults by a Needle-Free Injection System
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DOI：
10.1128/cvi.00167-08
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发表时间：
2008-11-01
影响因子：
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通讯作者：
Koelle, David M.
中科院分区：
文献类型：
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作者：
Cattamanchi, Ashok;Posavad, Christine M.;Koelle, David M.
我们进行了一项双盲、溶剂对照、剂量递增的安全性和免疫原性试验，试验对象为通过无针装置接种的候选单纯疱疹病毒2型（HSV-2）表面糖蛋白D2（gD 2）DNA疫苗。62名健康成人按4：1的疫苗与安慰剂比例随机分组。一半的参与者为HSV-1血清阴性，所有参与者均为HSV-2血清阴性。疫苗剂量包括100 μ g、300 μ g、1，000 μ g或3，000 μ g表达gD 2蛋白的质粒。受试者在第0、4、8和24周接种疫苗。一些受试者在52周时接受了额外的1，000 μ g加强。我们发现疫苗是安全的，耐受性良好，大多数不良事件是局部反应。未观察到剂量限制性毒性。在第三次疫苗注射后2周，在接受3，000 μ g疫苗的4名HSV-1血清阴性、HSV-2血清阴性参与者中的1名中检测到gD 2特异性细胞毒性T淋巴细胞和淋巴细胞增殖反应。针对HSV-2的基于DNA的疫苗接种策略似乎是安全的，并且可能产生疫苗特异性细胞免疫应答，但是可能需要高疫苗剂量才能在大多数接种者中引发免疫应答。
We conducted a double-blind, vehicle-controlled, dose escalation safety and immunogenicity trial of a candidate herpes simplex virus type 2 (HSV-2) surface glycoprotein D2 (gD2) DNA vaccine administered by use of a needle-free device. Sixty-two healthy adults were randomized using a 4:1 vaccine-to-placebo ratio. Half of the participants were HSV-1 seronegative, and all were HSV-2 seronegative. Vaccine doses included 100 mu g, 300 mu g, 1,000 mu g or 3,000 mu g of a plasmid expressing the gD2 protein. Subjects received vaccine at 0, 4, 8, and 24 weeks. Some subjects received an additional 1,000-mu g boost at 52 weeks. We found that the vaccine was safe and well tolerated, with most adverse events being local site reactions. No dose-limiting toxicities were observed. gD2-specific cytotoxic T-lymphocyte and lymphoproliferation responses were detected 2 weeks after the third vaccine injection in one of four HSV-1-seronegative, HSV-2-seronegative participants who received 3,000 mu g of vaccine. A DNA-based vaccination strategy against HSV-2 appears to be safe and may generate a vaccine-specific cellular immune response, but high vaccine doses are likely needed to elicit an immune response in most vaccinees.