Infusion of bispecific monoclonal antibody complexes into monkeys providesimmunologic protection against later challenge with a model pathogen

Heteropolymers (HP), bispecific mAbs which bind target pathogens to primate erythrocytes via complement receptor 1, facilitate clearance of pathogens from the bloodstream by targeting them for destruction in the liver without causing lysis or clearance of the erythrocytes. We show that when HP prepa red with mouse IgG are intravenously infused into monkeys one or more times prior to exposure to a prototype pathogen, they bind to erythrocytes and r emain in the circulation long enough to act as "sentinels," preventing path ogen invasion of the bloodstream. The effectiveness of HP as sentinels is l imited both by the monkey's immune response to the HP and, prior to the imm une response, by a gradual loss of the HP from monkey erythrocytes over a p eriod of 1 week, and we have investigated possible causes of this HP loss. In overview, our results suggest that HP prepared with mouse IgG are able t o effectively function as sentinels for a minimum of 4 days and, after repe at infusion, possibly for up to 2 weeks, (C) 1999 Academic Press.