Passive immunization with a human immunodeficiency virus type 1-neutralizing monoclonal antibody in Hu-PBL-SCID mice: isolation of a neutralization escape variant

Abstract

A monoclonal antibody (694/98-D) directed toward the V3 loop of human immunodeficiency virus type 1 (HIV-1) was evaluated for pre- and postexposure prophylaxis in SCID mice reconstituted with human peripheral blood lymphocytes (Hu-PBL-SCID). Fifty percent protection against the HIV-1LAI strain was obtained by preexposure administration of 1.32 mg/kg antibody. However, virus isolated from 1 mouse 3 weeks after passive immunization with 13.2 mg/kg antibody proved resistant to subsequent in vitro neutralization by 694/98-D. V3 loop sequence analysis of cloned virus revealed amino acid changes within the linear core epitope recognized by 694/98-D and in one flanking amino acid. Further evaluation of 694/98-D for postexposure prophylaxis in mice revealed that 694/ 98-D was effective when given 15 min after virus. However, efficacy declined to 50% if treatment was delayed to 1 h after virus inoculation. These studies point out some potential drawbacks of passive immunization with monoclonal antibodies.