PASSIVE-IMMUNIZATION WITH A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-NEUTRALIZING MONOCLONAL-ANTIBODY IN HU-PBL-SCID MICE - ISOLATION OF A NEUTRALIZATION ESCAPE VARIANT

A monoclonal antibody (694/98-D) directed toward the V3 loop of human immunodeficiency virus type 1 (HTV-1) was evaluated for pre-and postex posure prophylaxis in SCID mice reconstituted with human peripheral bl ood lymphocytes (Hu-PBL-SCID). Fifty percent protection against the HI V-1(LAI) strain was obtained by preexposure administration of 1.32 mg/ kg antibody, However, virus isolated from I mouse 3 weeks after passiv e immunization with 13.2 mg/kg antibody proved resistant to subsequent in vitro neutralization by 693/98-D. V3 loop sequence analysis of clo ned virus revealed amino acid changes within the linear core epitope r ecognized by 694/98-D and in one flanking amino acid. Further evaluati on of 693/98-D for postexposure prophylaxis in mice revealed that 694/ 98-D was effective when given 15 min after virus. However, efficacy de clined to 50% if treatment was delayed to 1 h after virus inoculation. These studies point out some potential drawbacks of passive immunizat ion with monoclonal antibodies.