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Utility of the Sindbis replicon system as an Env-targeted HIV vaccine.

机译：Sindbis复制系统可作为针对Env的HIV疫苗。

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Sindbis replicon-based vaccine vectors are designed to combine the immunostimulatory properties of replicating viruses with the superior safety profile of non-replicating systems. In this study we performed a detailed assessment of Sindbis (SIN) replicon vectors expressing HIV-1 envelope protein (Env) for the induction of cell-mediated and humoral immune responses in a small animal model. SIN-derived virus-like particles (VLP) elicited Env-specific antibody responses that were detectable after boosting with recombinant Env protein. This priming effect could be mediated by replicon activity alone but may be enhanced by Env attached to the surface of VLP, offering a potential advantage for this mode of replicon delivery for Env based vaccination strategies. In contrast, the Env-specific CTL responses that were elicited by SIN-VLP were entirely dependent on replicon activity. SIN-VLP priming induced more durable humoral responses than immunization with protein only. This is important from a vaccine perspective, given the intrinsic tendency of Env to induce short-lived antibody responses in the context of vaccination or infection. These results indicate that further efforts to enhance the magnitude and durability of the HIV-1 Env-specific immune responses generated by Sindbis vectors, either alone or as part of prime-boost regimens, are justified.
机译：设计基于Sindbis复制子的疫苗载体，将复制病毒的免疫刺激特性与非复制系统的卓越安全性相结合。在这项研究中，我们对表达HIV-1包膜蛋白（Env）的Sindbis（SIN）复制子载体进行了详细评估，以在小动物模型中诱导细胞介导的体液免疫反应。 SIN衍生的病毒样颗粒（VLP）引发了Env特异性抗体应答，在重组Env蛋白加强免疫后可检测到。此引发作用可能仅通过复制子活性来介导，但可以通过附着在VLP表面的Env增强，从而为基于Env的疫苗接种策略提供这种复制子传递方式潜在的优势。相反，由SIN-VLP引起的Env特异的CTL反应完全取决于复制子的活性。与仅用蛋白质免疫相比，SIN-VLP引发引发更持久的体液反应。从疫苗的角度来看，这很重要，因为在疫苗接种或感染的情况下，Env具有诱导短期抗体应答的内在趋势。这些结果表明，有必要进一步努力提高由Sindbis载体单独或作为初免-加强疗法的一部分而产生的HIV-1 Env特异性免疫应答的强度和持久性。

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