title: An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza A antibodies.
abstract: Recent advances enabling the cloning of human immunoglobulin G genes have proven effective for discovering monoclonal antibodies with therapeutic potential. However, these antibody-discovery methods are often arduous and identify only a few candidates from numerous antibody-secreting plasma cells or plasmablasts. We describe an in vivo enrichment technique that identifies broadly neutralizing human antibodies with high frequency. For this technique, human peripheral blood mononuclear cells from vaccinated donors are activated and enriched in an antigen-specific manner for the production of numerous antigen-specific plasmablasts. Using this technology, we identified four broadly neutralizing influenza A antibodies by screening only 840 human antibodies. Two of these antibodies neutralize every influenza A human isolate tested and perform better than the current anti-influenza A therapeutic, oseltamivir, in treating severe influenza infection in mice and ferrets. Furthermore, these antibodies elicit robust in vivo synergism when combined with oseltamivir, thus highlighting treatment strategies that could benefit influenza-infected patients.
authors.affiliation: Antibody Engineering Department, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Nakamura
authors.forename: Ning
authors.initials: N
authors.lastname: Chai
authors.forename: Summer
authors.initials: S
authors.lastname: Park
authors.forename: Nancy
authors.initials: N
authors.lastname: Chiang
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Lin
authors.forename: Henry
authors.initials: H
authors.lastname: Chiu
authors.forename: Rina
authors.initials: R
authors.lastname: Fong
authors.forename: Donghong
authors.initials: D
authors.lastname: Yan
authors.forename: Janice
authors.initials: J
authors.lastname: Kim
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.forename: Alberto
authors.initials: A
authors.lastname: Estevez
authors.forename: Mary
authors.initials: M
authors.lastname: Coons
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Patrick
authors.initials: P
authors.lastname: Lupardus
authors.forename: Mercedesz
authors.initials: M
authors.lastname: Balazs
authors.forename: Lee R
authors.initials: LR
authors.lastname: Swem
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D005289:Ferrets; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology*; D007251:Influenza, Human / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009500:Neutralization Tests / Q000379:methods*; D010950:Plasma Cells / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G