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Generation of recombinant hyperimmune globulins from diverse B-cell repertoires.

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.

SUBMITTER: Keating SM

PROVIDER: S-EPMC8355030 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Generation of recombinant hyperimmune globulins from diverse B-cell repertoires.

Keating Sheila M SM Mizrahi Rena A RA Adams Matthew S MS Asensio Michael A MA Benzie Emily E Carter Kyle P KP Chiang Yao Y Edgar Robert C RC Gautam Bishal K BK Gras Ashley A Leong Jackson J Leong Renee R Lim Yoong Wearn YW Manickam Vishal A VA Medina-Cucurella Angelica V AV Niedecken Ariel R AR Saini Jasmeen J Simons Jan Fredrik JF Spindler Matthew J MJ Stadtmiller Kacy K Tinsley Brendan B Wagner Ellen K EK Wayham Nicholas N Tracy LaRee L Lundberg Carina Vingsbo CV Büscher Dirk D Terencio Jose Vicente JV Roalfe Lucy L Pearce Emma E Richardson Hayley H Goldblatt David D Ramjag Anushka T AT Carrington Christine V F CVF Simmons Graham G Muench Marcus O MO Chamow Steven M SM Monroe Bryan B Olson Charles C Oguin Thomas H TH Lynch Heather H Jeanfreau Robert R Mosher Rachel A RA Walch Matthew J MJ Bartley Christopher R CR Ross Carl A CA Meyer Everett H EH Adler Adam S AS Johnson David S DS

Nature biotechnology 20210415 8

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 the ...[more]

PMID: 33859400

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Project description:Background:Biogas production is an attractive technology for a sustainable generation of renewable energy. Although the microbial community is fundamental for such production, the process control is still limited to technological and chemical parameters. Currently, most of the efforts on microbial management system (MiMaS) are focused on process-specific marker species and community dynamics, but a practical implementation is in its infancy. The high number of unknown and uncharacterized microorganisms in general is one of the reasons hindering further advancements. Results:A Biogas Metagenomics Hybrid Assembly (BioMETHA) database, derived from microbiomes of biogas plants, was generated using a dedicated assembly strategy for different metagenomic datasets. Long reads from nanopore sequencing (MinION) were combined with short, more accurate second-generation sequencing reads (Illumina). The hybrid assembly resulted in 231 genomic bins each representing a taxonomic unit with an average completeness of 47%. Functional annotation identified 13,190 non-redundant genes covering roughly 207 k coding sequences. Mapping rates of metagenomics DNA derived from diverse biogas plants and laboratory reactors increased up to 73%. In addition, an EC (enzyme commission) reference sequence collection (ERSC) was generated whose genes are crucial for biogas-related processes, consisting of 235 unique EC numbers organized in 52 metabolic modules. Mapping rates of metatranscriptomic data to this ERSC revealed coverages of up to 93%. Process parameters and imbalances of laboratory reactors could be reconstructed by evaluating abundance of biogas-specific metabolic modules using metatranscriptomic data derived from various fermenter systems. Conclusion:This newly established metagenomic hybrid assembly in combination with an EC reference sequence collection might help to shed light on the microbial dark matter of biogas plants by contributing to the development of a reference for biogas plant microbiome-specific gene sequences. Considering a biogas microbiome as a complex meta-organism expressing a meta-transcriptome, the approach established here could lay the foundation for a function-based microbial management system.

Dataset Information

Generation of recombinant hyperimmune globulins from diverse B-cell repertoires.

Publications

Generation of recombinant hyperimmune globulins from diverse B-cell repertoires.

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