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首页> 外文期刊>Vaccine >An HIV-based lentiviral vector as HIV vaccine candidate: immunogenic characterization.
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An HIV-based lentiviral vector as HIV vaccine candidate: immunogenic characterization.

机译：基于HIV的慢病毒载体作为HIV疫苗候选者：免疫原性表征。

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Recently developed viral-vectored HIV vaccine candidates, despite achieving high levels transgene expression and inducing high magnitude immune responses to HIV, have faced limitations related to anti-vector immunity. In contrast, lentiviral vectors (LV) have been shown to be less sensitive to anti-vector neutralizing activity, while displaying desirable characteristics, such as transduction of non-dividing cells, including antigen-presenting cells, and long-term transgene expression. We have developed VRX1023, an HIV-based LV expressing HIV Gag, Pol and Rev under the control of the native HIV LTR. In mice, this vector induced significant mucosal and systemic cellular and humoral responses against HIV after sub-cutaneous injection. Similarly to other viral vectors, this LV candidate can be effectively used in DNA prime, LV boost strategies, where it elicited as high as 21% HIV Gag-specific CD8 responses as measured by intracellular cytokine staining. Moreover, anti-vector immunity is not an obstacle to repeated LV administrations, as shown by improved anti-HIV responses compared to single LV immunization. In head to head comparisons with Ad5 vectors expressing the same vaccine payload, VRX1023 elicited higher and more persistent cellular and antibody responses to HIV than its adenoviral counterpart. In preparation for clinical use, manufacturing scale-up of a highly purified VRX1023 vector lot following cGMP was successfully achieved without altering the robust immunogenicity observed with the research-grade vector. VRX1023, in addition to competing favorably with existing vectors such as Ad5 for anti-HIV immune responses, demonstrates unique features likely to address some of the pitfalls of current vector-based HIV vaccine strategies.
机译：尽管已经实现了高水平的转基因表达并诱导了对HIV的高度免疫反应，但最近开发的病毒载体HIV疫苗候选物却面临着与抗载体免疫有关的局限性。相反，慢病毒载体（LV）已显示出对抗载体中和活性较不敏感，同时显示出所需的特征，例如转导包括抗原呈递细胞在内的非分裂细胞，以及长期转基因表达。我们已经开发了VRX1023，这是一种在原始HIV LTR的控制下表达HIV Gag，Pol和Rev的基于HIV的LV。在小鼠中，皮下注射后，该载体可诱导针对HIV的明显的粘膜和全身细胞及体液反应。与其他病毒载体相似，这种LV候选物可以有效地用于DNA初免，LV增强策略，通过细胞内细胞因子染色测量，它可以引发高达21％的HIV Gag特异性CD8反应。而且，抗载体免疫力不是重复进行LV给药的障碍，与单LV免疫相比，抗HIV应答得到改善。在与表达相同疫苗有效载荷的Ad5载体进行的正面对比中，VRX1023引起的对HIV的细胞和抗体应答比其腺病毒对应物更高，更持久。在为临床使用做准备时，成功实现了cGMP之后高纯度VRX1023载体批次的大规模生产，而不会改变研究级载体所观察到的强大免疫原性。 VRX1023除了可以与现有的载体（例如Ad5）竞争抗HIV免疫反应外，还具有独特的功能，可以解决当前基于载体的HIV疫苗策略中的一些陷阱。

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