Successful immunization with a single injection of non-integrating lentiviral vector
Successful immunization with a single injection of non-integrating lentiviral vector
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DOI：
10.1038/sj.mt.6300241
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发表时间：
2007-09-01
影响因子：
12.4
通讯作者：
Cara, Andrea
中科院分区：
文献类型：
--
作者：
Negri, Donatella R. M.;Michelini, Zuleika;Cara, Andrea
我们评估了整合酶(IN)缺陷的自失活慢病毒载体(SinLV)在小鼠体内传递人类免疫缺陷病毒-1(HIV-1)包膜序列以诱导特异性免疫反应的能力。用表达HIV-1(JR-FL)gp120密码子优化序列的IN缺陷型sinLV一次肌肉注射免疫BALB/c小鼠，并将结果与IN不能胜任的相同序列的结果进行比较。在未整合到宿主基因组的情况下，IN缺陷型sinLV在免疫后90天内可诱导特异性和持久性的免疫应答，免疫后90天，脾细胞和骨髓细胞中的干扰素-γ(IFN-γ)检测、脾细胞中的铬释放试验和血清中的抗体检测均可检测到干扰素-γ。这些数据提供的证据表明，在没有载体整合的情况下，一次注射IN缺陷的sinLV可以引起显着的免疫反应，可能是一种安全和有用的疫苗开发策略。
We evaluated the ability of an integrase ( IN)-defective self-inactivating lentiviral vector ( sinLV) for the delivery of human immunodeficiency virus-1( HIV-1) envelope sequences in mice to elicit specific immune responses. BALB/c mice were immunized with a single intramuscular injection of the IN-defective sinLV expressing the codon optimized HIV-1(JR-FL) gp120 sequence, and results were compared with those for the IN-competent counterpart. The IN-defective sinLV elicited specific and longlasting immune responses, as evaluated up to 90 days from the immunization by enzyme-linked immunosorbent spot ( ELISPOT) and intracellular staining ( ICS) for interferon-gamma( IFN-gamma) assays in both splenocytes and bone marrow ( BM) cells, chromium release assay in splenocytes, and antibody detection in sera, without integration of the vector into the host genome. These data provide evidence that a single administration of an IN-defective sinLV elicits a significant immune response in the absence of vector integration and may be a safe and useful strategy for vaccine development.