美国GigaGen公司David S. Johnson团队从不同的B细胞库中生成重组的超免疫球蛋白。相关论文于2021年4月15日在线发表于国际学术期刊《自然—生物技术》。

研究人员报道了一种微流控和分子基因组学策略，可用于捕获各种哺乳动物抗体库来创建重组多价超免疫球蛋白。这个方法产生了数千种重组抗体的多种混合物，这些混合物针对治疗靶点的特异性和活性得到了富集。每种超免疫球蛋白产品均包含成千上万的抗体，这些抗体来自恢复期或接种疫苗的人类供体或免疫小鼠。

使用这种方法，研究人员在不到3个月的时间内就产生了对SARS-CoV-2具有强力中和活性的超免疫球蛋白，专为Zika病毒而设计的Fc工程化超免疫球蛋白，其缺乏抗体依赖性疾病的增强作用，原发性免疫缺陷患者肺病原体特异的超免疫球蛋白。为了解决兔来源的抗胸腺细胞球蛋白的局限性，研究人员生成了重组的人类版本，并证明了其在小鼠中对移植物抗宿主病的功效。

据介绍，血浆来源的多克隆抗体疗法，例如静脉内免疫球蛋白，具有多个缺点，包括效力低、杂质、供应不足和批次间差异。

附：英文原文

Title: Generation of recombinant hyperimmune globulins from diverse B-cell repertoires

Author: Sheila M. Keating, Rena A. Mizrahi, Matthew S. Adams, Michael A. Asensio, Emily Benzie, Kyle P. Carter, Yao Chiang, Robert C. Edgar, Bishal K. Gautam, Ashley Gras, Jackson Leong, Renee Leong, Yoong Wearn Lim, Vishal A. Manickam, Angelica V. Medina-Cucurella, Ariel R. Niedecken, Jasmeen Saini, Jan Fredrik Simons, Matthew J. Spindler, Kacy Stadtmiller, Brendan Tinsley, Ellen K. Wagner, Nicholas Wayham, LaRee Tracy, Carina Vingsbo Lundberg, Dirk Bscher, Jose Vicente Terencio, Lucy Roalfe, Emma Pearce, Hayley Richardson, David Goldblatt, Anushka T. Ramjag, Christine V. F. Carrington, Graham Simmons, Marcus O. Muench, Steven M. Chamow, Bryan Monroe, Charles Olson, Thomas H. Oguin, Heather Lynch, Robert Jeanfreau, Rachel A. Mosher, Matthew J. Walch, Christopher R. Bartley, Carl A. Ross, Everett H. Meyer, Adam S. Adler, David S. Johnson

Issue&Volume: 2021-04-15

Abstract: Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply and batch-to-batch variation. Here we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates of diverse mixtures of thousands of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors or from immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in under 3months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease.

DOI: 10.1038/s41587-021-00894-8

Source: https://www.nature.com/articles/s41587-021-00894-8