BISPECIFIC MONOCLONAL-ANTIBODY COMPLEXES FACILITATE ERYTHROCYTE BINDING AND LIVER CLEARANCE OF A PROTOTYPE PARTICULATE PATHOGEN IN A MONKEYMODEL

We used Anger camera imaging in a monkey model to investigate the orga n localization of a prototype particulate pathogen, (131)l-labeled bac teriophage phi X174, after it was bound to the primate erythrocyte com plement receptor and then cleared from the circulation. This (131)l-la beled phi X174 was infused into the circulation of an immunized monkey , and the nascently formed immune complexes showed rapid and quantitat ive binding to erythrocytes via the immune adherence reaction (complem ent-mediated binding). Alternatively, phi X174 was infused into the ci rculation of a naive animal, and then cross-linked bispecific mAb comp lexes (heteropolymers, anti-CR1 x anti-phi X174) were infused into the circulation. The infused heteropolymers also facilitated rapid and qu antitative 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 clea red to the liver, with a small amount clearing to the spleen. Further liver imaging confirmed that within 24 h most of the bacteriophage pre viously cleared to the liver via the heteropolymer system was phagocyt osed and destroyed, The findings in this model system provide addition al evidence for the potential utility of heteropolymers to facilitate the safe and rapid clearance of blood-borne pathogens as a potential t reatment for infectious diseases.