Bispecific monoclonal antibody complexes facilitate erythrocyte binding and liver clearance of a prototype particulate pathogen in a monkey model.
We used Anger camera imaging in a monkey model to investigate the organ localization of a prototype particulate pathogen, 131I-labeled bacteriophage phi X174, after it was bound to the primate erythrocyte complement receptor and then cleared from the circulation. This 131I-labeled phi X174 was infused into the circulation of an immunized monkey, and the nascently formed immune complexes showed rapid and quantitative binding to erythrocytes via the immune adherence reaction (complement-mediated binding). Alternatively, phi X174 was infused into the circulation of a naive animal, and then cross-linked bispecific mAb complexes (heteropolymers, anti-CR1 x anti-phi X174) were infused into the circulation. The infused heteropolymers also facilitated rapid and quantitative binding of phi X174 to erythrocytes. In both cases, after a short lag period, the erythrocyte-bound phi X174 was rapidly cleared from the circulation, and the vast majority of the radiolabel was cleared to the liver, with a small amount clearing to the spleen. Further liver imaging confirmed that within 24 h most of the bacteriophage previously cleared to the liver via the heteropolymer system was phagocytosed and destroyed. The findings in this model system provide additional evidence for the potential utility of heteropolymers to facilitate the safe and rapid clearance of blood-borne pathogens as a potential treatment for infectious diseases.
Taylor
R P
RP
Department of Biochemistry, University of Virginia School of Medicine, Charlottesville 22908, USA.
Martin
E N
EN
Reinagel
M L
ML
Nardin
A
A
Craig
M
M
Choice
Q
Q
Schlimgen
R
R
Greenbaum
S
S
Incardona
N L
NL
Ochs
H D
HD
D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000032:analysis; D010584:Bacteriophage phi X 174 / Q000276:immunology* / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007104:Immune Adherence Reaction; D007141:Immunoglobulin Fc Fragments / Q000502:physiology; D007262:Infusions, Intravenous; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D008251:Macaca; D008252:Macaca fascicularis; D008954:Models, Biological; D017463:Receptors, Complement 3b / Q000378:metabolism; D014771:Virion / Q000276:immunology / Q000378:metabolism
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D007141:Immunoglobulin Fc Fragments; D017463:Receptors, Complement 3b