Multifunctional T-cell characteristics induced by a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 vaccine regimen given to healthy adults are dependent on the route and dose of administration
Multifunctional T-cell characteristics induced by a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 vaccine regimen given to healthy adults are dependent on the route and dose of administration
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DOI：
10.1128/jvi.00068-08
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发表时间：
2008-07-01
影响因子：
5.4
通讯作者：
Goepfert, Paul A.
中科院分区：
文献类型：
--
作者：
Bansal, Anju;Jackson, Bethany;Goepfert, Paul A.
一项1期临床疫苗研究表明，针对血清阴性成人的1型人类免疫缺陷病毒（HIV-1）疫苗方案（包括DNA初免制剂（5价env和单价gag），随后进行5价Env蛋白加强）可诱导HIV-1特异性T细胞和能够中和交叉进化枝病毒分离株的抗Env抗体。根据这些初步发现，我们试图通过使用多色流式细胞术更全面地表征HIV-1特异性T细胞。三组参与者用皮内施用的1.2mg DNA接种三次（i.d.; A组：肌肉注射DNA 1.2mg; B组），或肌肉注射7.2mg DNA。C组（高剂量组）。每组随后接受一剂或两剂0.375 mg gp 120蛋白加强疫苗（i.m.）。在大多数参与者中观察到Env特异性CD 4 T细胞应答;然而，应答的动力学取决于DNA给药途径。高M。剂量在DNA疫苗接种后诱导最大幅度的反应，而i.d.组表现出最小幅度的反应。然而，在第二次蛋白质加强后，i.d.组与其他两组无明显区别。在DNA疫苗接种和第一次蛋白质加强后，在高剂量组中观察到比其他组更多数量的多功能Env特异性CD 4 T细胞（具有>= 2种功能的那些）。仅在高剂量组中观察到Gag特异性CD 4 T细胞和Env特异性CD 8 T细胞。这些发现表明，DNA疫苗的途径和剂量显著影响免疫应答的质量，为未来的疫苗设计提供了重要信息。
A phase 1 clinical vaccine study of a human immunodeficiency virus type 1 (HIV-1) vaccine regimen comprising a DNA prime formulation (5-valent env and monovalent gag) followed by a 5-valent Env protein boost for seronegative adults was previously shown to induce HIV-1-specific T cells and anti-Env antibodies capable of neutralizing cross-clade viral isolates. In light of these initial findings, we sought to more fully characterize the HIV-1-specific T cells by using polychromatic How cytometry. Three groups of participants were vaccinated three times with 1.2 mg of DNA administered intradermally (i.d.; group A), 1.2 mg of DNA administered intramuscularly (i.m.; group B), or 7.2 mg of DNA administered i.m. (high-dose group C) each time. Each group subsequently received one or two doses of 0.375 mg each of the gp120 protein boost vaccine (i.m.). Env-specific CD4 T-cell responses were seen in the majority of participants; however, the kinetics of responses differed depending on the route of DNA administration. The high i.m. dose induced the responses of the greatest magnitude after the DNA vaccinations, while the i.d. group exhibited the responses of the least magnitude. Nevertheless, after the second protein boost, the magnitude of CD4 T-cell responses in the i.d. group was indistinguishable from those in the other two groups. After the DNA vaccinations and the first protein boost, a greater number of polyfunctional Env-specific CD4 T cells (those with >= 2 functions) were seen in the high-dose group than in the other groups. Gag-specific CD4 T cells and Env-specific CD8 T cells were seen only in the high-dose group. These findings demonstrate that the route and dose of DNA vaccines significantly impact the quality of immune responses, yielding important information for future vaccine design.