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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Enhanced neutralization of HIV by antibodies displayed on the S-layer of Caulobacter crescentus.
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Enhanced neutralization of HIV by antibodies displayed on the S-layer of Caulobacter crescentus.

机译：显示在新月形杆菌S层上的抗体增强的HIV中和作用。

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Innovative methods of prevention are needed to stop the more than two million new HIV-1 infections annually, particularly in women. Local application of anti-HIV antibodies has been shown to be effective at preventing infection in nonhuman primates; however, the concentrations needed are cost prohibitive. Display of antibodies on a particulate platform will likely prolong effectiveness of these anti-HIV agents and lower the cost of goods. Here, we demonstrate that the bacterium Caulobacter crescentus and its highly expressed surface-layer (S-layer) protein can provide this antibody display platform. Caulobacters displaying protein G, alone or with CD4 codisplay, successfully captured HIV-1-specific antibodies and demonstrated functional neutralization. Compared to soluble antibodies, a neutralizing anti-HIV antibody displayed on Caulobacter was as effective or more effective at neutralizing diverse HIV-1 isolates. Moreover, when an antibody reactive with an epitope induced by CD4 binding (CD4i) was codisplayed with CD4, there was significant enhancement in HIV-1 neutralization. These results suggest that caulobacters displaying anti-HIV antibodies offer a distinct improvement in the use of antibodies as microbicides. Furthermore, these reagents can specifically evaluate anti-HIV antibodies in concert with other HIV-1 blocking agents to assess the most suitable tools for conversion to scFvs, allowing for direct display within the S-layer protein and further reducing cost of goods. In summary, C. crescentus, which can be easily produced and chemically stabilized at low cost, is well suited for engineering as an effective platform, offering an inexpensive way to produce and deliver HIV-1-specific microbicides.
机译：需要创新的预防方法来阻止每年超过200万的新HIV-1感染，尤其是在女性中。已显示局部使用抗HIV抗体可有效预防非人类灵长类动物的感染;然而，所需的浓度是禁止成本的。在颗粒状平台上展示抗体可能会延长这些抗HIV剂的有效性并降低商品成本。在这里，我们证明细菌新月形杆菌及其高度表达的表面层（S层）蛋白可以提供此抗体展示平台。单独或与CD4共展示展示蛋白质G的杆状细菌成功捕获了HIV-1特异性抗体并显示出功能中和作用。与可溶性抗体相比，展示在杆状细菌上的中和抗HIV抗体在中和各种HIV-1分离株方面同样有效或更有效。此外，当与CD4结合诱导的抗原决定簇（CD4i）反应的抗体与CD4共展示时，HIV-1中和作用显着增强。这些结果表明，展示抗HIV抗体的花杆菌在使用抗体作为杀微生物剂方面提供了明显的改善。此外，这些试剂可以与其他HIV-1阻断剂一起特异性评估抗HIV抗体，以评估最适合转化为scFv的工具，从而可以在S层蛋白中直接展示，从而进一步降低商品成本。总之，C.crescentus可以轻松生产并以低成本化学稳定，非常适合作为有效平台进行工程设计，从而提供了一种廉价的方式来生产和输送HIV-1特异杀微生物剂。

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