A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice
A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice
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DOI：
10.1073/pnas.152313899
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发表时间：
2002-07-23
影响因子：
11.1
通讯作者：
Hone, DM
中科院分区：
文献类型：
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作者：
Agwale, SM;Shata, MT;Hone, DM
要合理设计针对HIV-1的新疗法，就必须更好地了解大多数感染者对HIV-1产生无效免疫反应的机制。该报告显示，与单独编码gp120的DNA疫苗诱导的小鼠相比，接种双链gp120- tat DNA疫苗的小鼠CD8(+) T细胞对gp120的反应大大降低。后者诱导的CD8(+) T细胞反应包括强大的gp120特异性ifn - γ分泌和针对牛痘-env假型攻击的保护性抗病毒免疫。Tat对CD8(+) T细胞反应的影响程度取决于Tat的生物活性。因此，一种表达gp120和LTR激活的截断Tat缺陷的双链DNA疫苗引发了对gp120强烈的分泌ifn - γ的CD8(+) T细胞反应，但对牛痘环境的攻击仅具有边缘保护作用。然而，在接种双链gp120-Tat DNA疫苗之前，用灭活的Tat蛋白免疫可以完全阻断Tat的作用。
The rational design of new therapies against HIV-1 necessitates an improved understanding of the mechanisms underlying the production of ineffective immune responses to HIV-1 in most infected individuals. This report shows that the CD8(+) T cell responses to gp120 were greatly diminished in mice vaccinated with a bicistronic gp120-Tat DNA vaccine, compared with those induced by a DNA vaccine encoding gp120 alone. The CD8(+) T cell responses induced by the latter included strong gp120-specific IFN-gamma-secretion and protective antiviral immunity against challenge by a vaccinia-env pseudotype. The degree to which Tat influenced CD8(+) T cell responses depended on the bioactivity of Tat. Thus, a bicistronic DNA vaccine that expresses gp120 and a truncated Tat defective for LTR activation elicited strong IFN-gamma-secreting CD8(+) T cell responses to gp120 but conferred only marginal protection against the vaccinia-env challenge. The effect of Tat was completely blocked, however, by immunization with inactivated Tat protein before vaccination with the bicistronic gp120-Tat DNA vaccine.