Generation of recombinant hyperimmune globulins from diverse B-cell repertoires
| Autor: | Christine V.F. Carrington, Steven M Chamow, Adam S. Adler, Matthew Adams, Sheila M. Keating, Emma Pearce, Ashley Gras, Robert C. Edgar, Charles Olson, Dirk Büscher, Jasmeen Saini, Kyle P Carter, Ariel R Niedecken, Heather E. Lynch, Rachel Mosher, Ellen K. Wagner, Vishal A. Manickam, Renee Leong, Bishal K. Gautam, Jan Fredrik Simons, Marcus O. Muench, Matthew J. Spindler, Jose Vicente Terencio, LaRee Tracy, Brendan Tinsley, Thomas H. Oguin, David S. Johnson, Yao Chiang, Nicholas Wayham, Everett Meyer, Rena A. Mizrahi, Anushka T. Ramjag, Carl A. Ross, Carina Vingsbo Lundberg, David Goldblatt, Matthew J Walch, Yoong Wearn Lim, Jackson Leong, Michael A. Asensio, Lucy Roalfe, Robert Jeanfreau, Emily Benzie, Christopher R. Bartley, Graham Simmons, Hayley Richardson, Bryan Monroe, Angélica V Medina-Cucurella, Kacy Stadtmiller |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Hyperimmune globulin
Globulin Biomedical Engineering Bioengineering Enzyme-Linked Immunosorbent Assay CHO Cells Antibodies Viral Applied Microbiology and Biotechnology Article law.invention 03 medical and health sciences Mice 0302 clinical medicine Immune system Cricetulus law medicine Animals Humans B cell COVID-19 Serotherapy 030304 developmental biology 0303 health sciences B-Lymphocytes biology SARS-CoV-2 Immunization Passive COVID-19 Globulins Zika Virus Virology Recombinant Proteins 3. Good health medicine.anatomical_structure Immunization Polyclonal antibodies biology.protein Recombinant DNA Molecular Medicine Antibody 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Nature biotechnology |
| ISSN: | 1546-1696 1087-0156 |
| Popis: | 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 thousands-diverse mixtures 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 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 three months, 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 (ATG), we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease. |
| Databáze: | OpenAIRE |
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