Protein A chromatography is one of the most widely used purification steps in the manufacturing of the various classes of recombinant and non-recombinant antibodies. Due to the higher cost, lower binding capacity, and limited life cycle of Protein A ligand, this affinity-based purification step is often one of the most significant contributors to the cost of manufacturing of monoclonal antibody (mAb) products. In the last decade, there has been significant progress in improving the Protein A chromatography throughput by designing new engineered Staphylococcal Protein A (SPA) variants with higher dynamic binding capacity, considerable alkaline tolerance, and mild acidic elution pH. This review aims at summarizing the various protein engineering approaches used for improving the throughput of the Protein A-based affinity purification of various immunoglobulins. With biopharmaceutical producers operating under ever-increasing pressure towards reducing the cost of manufacturing, these advances in engineered protein A variants will help in processing larger cell culture volumes with high throughput and thereby significantly lower the cost of raw materials.

蛋白A色谱是制造各种类型的重组和非重组抗体中最广泛使用的纯化步骤之一。由于蛋白A配体的较高成本，较低的结合能力和有限的生命周期，基于亲和力的纯化步骤通常是单克隆抗体（mAb）产品生产成本的最重要因素之一。在过去的十年中，通过设计新的工程葡萄球菌，在提高蛋白A色谱通量方面取得了重大进展。蛋白A（SPA）变体具有更高的动态结合能力，显着的耐碱性和温和的酸性洗脱pH。这篇综述旨在概述用于提高各种免疫球蛋白基于蛋白质A的亲和纯化的通量的各种蛋白质工程方法。随着生物制药生产商在降低生产成本的压力越来越大的情况下，工程蛋白A变体的这些进步将有助于以高通量处理更大的细胞培养量，从而显着降低原材料成本。