Calarota S, Bratt G, Nordlund S, Hinkula J, Leandersson A C, Sandström E, Wahren B
Microbiology and Tumourbiology Center, Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm.
Lancet. 1998 May 2;351(9112):1320-5. doi: 10.1016/S0140-6736(97)09440-3.
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.
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.
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.
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 non-selected or non-infected individuals. The small number of patients presented here does not allow generalisation of our findings.
已知DNA疫苗接种可在动物模型中产生针对HIV-1的免疫反应。我们旨在评估DNA疫苗接种在HIV-1感染的人类中诱导免疫反应的效果。
9名无症状的HIV-1感染患者用编码HIV-1 nef、rev或tat调节基因的DNA构建体进行免疫接种。这些患者被选择为对这些抗原没有或只有低抗体反应性。在6个月内的三次免疫接种之前、期间和之后，测量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。
在DNA免疫接种前，针对HIV-1调节蛋白的细胞免疫反应不存在或很低。DNA疫苗接种在所有患者中诱导出可检测到的记忆细胞，在8名患者中诱导出特异性细胞毒性。CTL受MHC-I类限制，主要来源于CD8+。在3名患者中，细胞活性是短暂的，在初始反应后下降。
用HIV-1基因进行DNA免疫接种可在人类中诱导特异性细胞反应，且无明显副作用。理论上，对调节蛋白的HIV-1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，我们选择的患者的反应可能比未选择或未感染的个体要小。这里展示的患者数量较少，无法将我们的发现推广。
