Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products.

传统多克隆抗体混合物中只有一小部分抗体可识别目标靶标，经常导致不良的多反应性。在这里，我们表明通过结合噬菌体和酵母菌展示，可以在体外轻松产生高质量的重组多克隆抗体，其中数百种不同的抗体全部针对目标靶标。我们显示出，与资源有限的传统多克隆抗体不同，重组多克隆抗体可以扩增超过一亿倍而不会失去代表性或功能性。我们对9种不同的靶标进行了测试，以证明该策略如何选择性地扩增针对所需靶标特异性表位的抗体，例如在一种蛋白质中发现的抗原，而不是紧密相关的一种，并消除识别常见表位的抗体，而不会显着丧失多样性。这些重组的可再生多克隆抗体可用于不同的测定中，并可以高通量产生。该方法可潜在地用于开发针对所有人类基因产物的高度特异性的重组可再生抗体。