Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients
Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients
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DOI：
10.1016/s0140-6736(97)09440-3
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发表时间：
1998-05-02
期刊：
影响因子：
168.9
通讯作者：
Wahren, B
中科院分区：
文献类型：
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作者：
Calarota, S;Bratt, G;Wahren, B
背景已知DNA疫苗接种在动物模型中产生针对HIV-1的免疫应答。我们的目的是评估DNA疫苗接种在诱导免疫反应的HIV-1感染humanbeings.Methods九个无病毒的HIV-1感染的患者进行免疫接种的DNA构建体编码的nef，rev，或达特调节基因的HIV-1。选择对这些抗原没有或具有低抗体反应性的患者。HIV-1特异性细胞毒性T淋巴细胞（CTL），前体频率，和抗原特异性增殖反应进行了测量之前，期间，和之后的三个免疫超过6 months.Findings细胞免疫反应对HIV-1调节蛋白的DNA免疫前不存在或低。DNA疫苗接种诱导可检测的记忆细胞在所有患者和特定的细胞毒性在8例。CTL是MHC-I类限制性的，并且主要是CD 8+来源。在三名患者的细胞活性是短暂的，减少后，最初的respons. Interpretation与HIV-1基因的DNA免疫可以诱导人类的特异性细胞反应，没有明显的副作用。从理论上讲，HIV-1对调节蛋白的特异性细胞毒性反应可能导致感染细胞在释放新病毒颗粒之前被清除。然而，有可能我们选择的患者的反应低于未选择或未感染的个体。这里介绍的患者数量较少，不能概括我们的发现。
Background DNA vaccination is known to generate immune responses against HIV-1 in animal models. We aimed to assess the efficacy of DNA vaccination in induction of immune responses in HIV-1-infected human beings.Methods Nine symptom-free HIV-1-infected patients were immunised with DNA constructs encoding the nef, rev, or tat regulatory genes of HIV-1. The patients were selected for having no or low antibody reactivities to these antigens. HIV-1-specific cytotoxic T-lymphocytes (CTLs), precursor frequencies, and antigen-specific proliferative responses were measured before, during, and after three immunisations over 6 months.Findings Cellular immune reactivities against the HIV-1 regulatory proteins were absent or low before DNA immunisation. DNA vaccination induced detectable memory cells in all patients and specific cytotoxicity in eight patients. CTLs were MHC-class-I restricted and mainly of CD8+ origin. In three patients the cellular activity was transient, decreasing after an initial response.Interpretation DNA immunisation with HIV-1 genes can induce specific cellular responses in human beings with no apparent side-effects. It is theoretically possible that HIV-1-specific cytotoxic responses to regulatory proteins could lead to infected cells being eliminated before they have released new viral particles. However, it is possible that the patients we selected responded less than would nonselected or non-infected individuals. The small number of patients presented here does not allow generalisation of our findings.