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Generation of recombinant hyperimmune globulins from diverse B-cell repertoires

Keating, SM; Mizrahi, RA; Adams, MS; Asensio, MA; Benzie, E; Carter, KP; Chiang, Y; ... Johnson, DS; + view all (2021) Generation of recombinant hyperimmune globulins from diverse B-cell repertoires. Nature Biotechnology , 39 pp. 989-999. 10.1038/s41587-021-00894-8. Green open access

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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 3 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, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease.

Type: Article
Title: Generation of recombinant hyperimmune globulins from diverse B-cell repertoires
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41587-021-00894-8
Publisher version: https://doi.org/10.1038/s41587-021-00894-8
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Applied immunology, Recombinant protein therapy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10126444
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