tetano
Editor, Senior Moderator
Nat Biotechnol
. 2021 Apr 15.
doi: 10.1038/s41587-021-00894-8. Online ahead of print.
Generation of recombinant hyperimmune globulins from diverse B-cell repertoires
Sheila M Keating[SUP] #[/SUP][SUP] 1 [/SUP], Rena A Mizrahi[SUP] #[/SUP][SUP] 1 [/SUP], Matthew S Adams[SUP] 1 2 [/SUP], Michael A Asensio[SUP] 1 [/SUP], Emily Benzie[SUP] 1 [/SUP], Kyle P Carter[SUP] 1 [/SUP], Yao Chiang[SUP] 1 [/SUP], Robert C Edgar[SUP] 1 [/SUP], Bishal K Gautam[SUP] 1 [/SUP], Ashley Gras[SUP] 1 [/SUP], Jackson Leong[SUP] 1 [/SUP], Renee Leong[SUP] 1 [/SUP], Yoong Wearn Lim[SUP] 1 [/SUP], Vishal A Manickam[SUP] 1 [/SUP], Angelica V Medina-Cucurella[SUP] 1 [/SUP], Ariel R Niedecken[SUP] 1 [/SUP], Jasmeen Saini[SUP] 1 [/SUP], Jan Fredrik Simons[SUP] 1 [/SUP], Matthew J Spindler[SUP] 1 [/SUP], Kacy Stadtmiller[SUP] 1 [/SUP], Brendan Tinsley[SUP] 1 [/SUP], Ellen K Wagner[SUP] 1 [/SUP], Nicholas Wayham[SUP] 1 [/SUP], LaRee Tracy[SUP] 3 [/SUP], Carina Vingsbo Lundberg[SUP] 4 [/SUP], Dirk B?scher[SUP] 5 [/SUP], Jose Vicente Terencio[SUP] 5 [/SUP], Lucy Roalfe[SUP] 6 [/SUP], Emma Pearce[SUP] 6 [/SUP], Hayley Richardson[SUP] 6 [/SUP], David Goldblatt[SUP] 6 [/SUP], Anushka T Ramjag[SUP] 7 [/SUP], Christine V F Carrington[SUP] 7 [/SUP], Graham Simmons[SUP] 8 [/SUP], Marcus O Muench[SUP] 8 [/SUP], Steven M Chamow[SUP] 9 [/SUP], Bryan Monroe[SUP] 9 [/SUP], Charles Olson[SUP] 9 [/SUP], Thomas H Oguin[SUP] 10 [/SUP], Heather Lynch[SUP] 10 [/SUP], Robert Jeanfreau[SUP] 11 [/SUP], Rachel A Mosher[SUP] 12 [/SUP], Matthew J Walch[SUP] 12 [/SUP], Christopher R Bartley[SUP] 12 [/SUP], Carl A Ross[SUP] 12 [/SUP], Everett H Meyer[SUP] 13 14 [/SUP], Adam S Adler[SUP] 1 [/SUP], David S Johnson[SUP] 15 [/SUP]
Affiliations
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.
. 2021 Apr 15.
doi: 10.1038/s41587-021-00894-8. Online ahead of print.
Generation of recombinant hyperimmune globulins from diverse B-cell repertoires
Sheila M Keating[SUP] #[/SUP][SUP] 1 [/SUP], Rena A Mizrahi[SUP] #[/SUP][SUP] 1 [/SUP], Matthew S Adams[SUP] 1 2 [/SUP], Michael A Asensio[SUP] 1 [/SUP], Emily Benzie[SUP] 1 [/SUP], Kyle P Carter[SUP] 1 [/SUP], Yao Chiang[SUP] 1 [/SUP], Robert C Edgar[SUP] 1 [/SUP], Bishal K Gautam[SUP] 1 [/SUP], Ashley Gras[SUP] 1 [/SUP], Jackson Leong[SUP] 1 [/SUP], Renee Leong[SUP] 1 [/SUP], Yoong Wearn Lim[SUP] 1 [/SUP], Vishal A Manickam[SUP] 1 [/SUP], Angelica V Medina-Cucurella[SUP] 1 [/SUP], Ariel R Niedecken[SUP] 1 [/SUP], Jasmeen Saini[SUP] 1 [/SUP], Jan Fredrik Simons[SUP] 1 [/SUP], Matthew J Spindler[SUP] 1 [/SUP], Kacy Stadtmiller[SUP] 1 [/SUP], Brendan Tinsley[SUP] 1 [/SUP], Ellen K Wagner[SUP] 1 [/SUP], Nicholas Wayham[SUP] 1 [/SUP], LaRee Tracy[SUP] 3 [/SUP], Carina Vingsbo Lundberg[SUP] 4 [/SUP], Dirk B?scher[SUP] 5 [/SUP], Jose Vicente Terencio[SUP] 5 [/SUP], Lucy Roalfe[SUP] 6 [/SUP], Emma Pearce[SUP] 6 [/SUP], Hayley Richardson[SUP] 6 [/SUP], David Goldblatt[SUP] 6 [/SUP], Anushka T Ramjag[SUP] 7 [/SUP], Christine V F Carrington[SUP] 7 [/SUP], Graham Simmons[SUP] 8 [/SUP], Marcus O Muench[SUP] 8 [/SUP], Steven M Chamow[SUP] 9 [/SUP], Bryan Monroe[SUP] 9 [/SUP], Charles Olson[SUP] 9 [/SUP], Thomas H Oguin[SUP] 10 [/SUP], Heather Lynch[SUP] 10 [/SUP], Robert Jeanfreau[SUP] 11 [/SUP], Rachel A Mosher[SUP] 12 [/SUP], Matthew J Walch[SUP] 12 [/SUP], Christopher R Bartley[SUP] 12 [/SUP], Carl A Ross[SUP] 12 [/SUP], Everett H Meyer[SUP] 13 14 [/SUP], Adam S Adler[SUP] 1 [/SUP], David S Johnson[SUP] 15 [/SUP]
Affiliations
- PMID: 33859400
- DOI: 10.1038/s41587-021-00894-8
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.