title: Bispecific monoclonal antibody complexes bound to primate erythrocyte complement receptor 1 facilitate virus clearance in a monkey model.
abstract: We investigated the feasibility of using bispecific mAb complexes to redirect and improve the efficiency of the primate E complement receptor 1-based clearance reaction to remove a virus from the circulation. As an initial approach, we used bacteriophage phiX174 as an immunologic model for mammalian viruses. Bispecific complexes were prepared by chemically cross-linking a mAb specific for complement receptor 1 with a mAb specific for the bacteriophage phiX174. In a monkey model these complexes facilitate rapid and quantitative binding of the target bacteriophage to E in vitro and in vivo. Moreover, after in vivo binding to E, the complexes containing mAb and prototype virus are rapidly cleared from the circulation of rhesus and cynomolgus monkeys without loss of E. Our findings suggest that bispecific mAb complexes, in concert with primate E complement receptor 1, may have therapeutic utility in the treatment of diseases associated with blood-borne pathogens.
authors.affiliation: Department of Biochemistry, University of Virginia School of Medicine, Charlottesville 22908, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Taylor
authors.forename: W M
authors.initials: WM
authors.lastname: Sutherland
authors.forename: E N
authors.initials: EN
authors.lastname: Martin
authors.forename: P J
authors.initials: PJ
authors.lastname: Ferguson
authors.forename: M L
authors.initials: ML
authors.lastname: Reinagel
authors.forename: E
authors.initials: E
authors.lastname: Gilbert
authors.forename: K
authors.initials: K
authors.lastname: Lopez
authors.forename: N L
authors.initials: NL
authors.lastname: Incardona
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology* / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D010584:Bacteriophage phi X 174 / Q000276:immunology*; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology* / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D011951:Receptors, Complement / Q000276:immunology* / Q000378:metabolism*; D014780:Viruses / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018033:Antibodies, Bispecific; D000936:Antigen-Antibody Complex; D011951:Receptors, Complement