A prototype pathogen bound ex vivo to human erythrocyte complement receptor 1 via bispecific monoclonal antibody complexes is cleared to the liver ina mouse model

Immune complexes (IC) bound to the primate erythrocyte (E) complement recep tor (CR1) are cleared from the circulation of primates and localized to the liver, le can be bound to E CR1 either via C3b opsonization or with cross- linked mAb complexes (heteropolymers, HP) which contain an mAb specific for CR-1 and a mAb specific for a prototype pathogen. The long-term goal of ou r work is to apply the HP to the treatment of human diseases associated wit h blood-borne pathogens. Therefore we have investigated the feasibility of a non-primate model by studying clearance in mice of bacteriophage Phi X174 bound via HP to primate E. E-HP-Phi X174 complexes were prepared in vitro and infused into the circulation of mice under conditions allowing short te rm survival of E ire the circulation. By radioimmunoassays and flow cytomet ry, we found that Phi X174 is removed from E and cleared from the circulati on coincident with loss of HP and CR1, and that the majority of cleared Phi X174 is localized to the liver. Through the use of HP constructed with Fab ' fragments, we verified the requirement for the Fc portion of the mAb in c learance; inhibition of C3 activation delayed clearance, suggesting a role for complement. The present findings in the mouse confirm previous observat ions in the non-human primate model.