Induction of antigen-specific CD8+T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine
Induction of antigen-specific CD8+T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine
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DOI：
10.1016/s0264-410x(00)00302-9
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发表时间：
2000-11-22
期刊：
影响因子：
5.5
通讯作者：
Fuller, DH
中科院分区：
文献类型：
--
作者：
Roy, MJ;Wu, MS;Fuller, DH
使用无针PowderJectTM系统将涂覆有DNA的金颗粒直接递送到皮肤细胞中，在12名健康的、未感染过肝炎的人类志愿者中评价抗B病毒（HBV）的DNA疫苗的安全性和免疫应答的诱导。三组四名志愿者接受了三种剂量水平（1，2或4 μ g）之一的编码HBV表面抗原的DNA的三次给药。该疫苗是安全的，耐受性良好，在接种部位仅引起一过性和轻度至中度反应。在每次免疫之前和之后测量HBV特异性抗体和CD 4+和CD 8 + T细胞应答。所有志愿者都产生了至少10 mIU/ml的保护性抗体应答。在HLA I类A2等位基因阳性的志愿者中，疫苗还诱导抗原特异性CD 8 + T细胞，其结合HLA-A2/HBsAg（335-343）四聚体，分泌IFN-γ，并裂解呈递肝炎B表面抗原（HBsAg）CTL表位的靶细胞。产生细胞因子的HBsAg特异性T细胞的计数表明优先诱导1型T辅助细胞应答。这些结果提供了DNA疫苗诱导保护性抗体滴度以及人类体液和细胞介导的免疫应答的首次证明。(C)2000爱思唯尔科技有限公司版权所有。
A DNA vaccine against the hepatitis B virus (HBV) was evaluated for safety and induction of immune responses in 12 healthy, hepatitis-naive human volunteers using the needle-free PowderJect(TM) system to deliver gold particles coated with DNA directly into cells of the skin. Three groups of four volunteers received three administrations of DNA encoding the surface antigen of HBV atone of the three dose levels (1, 2, or 4 mug). The vaccine was safe and well tolerated, causing only transient and mild to moderate responsesat the site of administration. HBV-specific antibody and both CD4 + and CD8 + T cell responses were measured before and after each immunization. All the volunteers developed protective antibody responses of at least 10 mIU/ml. In volunteers who were positive for the HLA class I A2 allele, the vaccine also induced antigen-specific CD8 + T cells that bound HLA-A2/HBsAg(335-343) tetramers, secreted IFN-gamma, and lysed target cells presenting a hepatitis B surface antigen (HBsAg) CTL epitope. Enumeration of HBsAg-specific T cells producing cytokine indicated preferential induction of a Type 1 T helper cell response. These results provide the first demonstration of a DNA vaccine inducing protective antibody titers and both humoral and cell-mediated immune responses in humans. (C) 2000 Elsevier Science Ltd. All rights reserved.