TY - JOUR
T1 - Passive immunization with a human immunodeficiency virus type 1- neutralizing monoclonal antibody in Hu-PBL-SCID mice
T2 - Isolation of a neutralization escape variant
AU - Andrus, Linda
AU - Prince, Alfred M.
AU - Bernal, Iscela
AU - McCormack, Patricia
AU - Lee, Dong Hun
AU - Gorny, Miroslaw K.
AU - Zolla-Pazner, Susan
N1 - Funding Information:
Received 2 July 1997; revised 30 October 1997. Animals were housed under conditions that met or exceeded the requirements of the NIH Guide for Care of Laboratory Animals. Financial support: American Foundation for AIDS Research (500118-10-PG); NIH (AI-34773, AI-32424, and AI-36085); M. K. Simpson Charitable Trust; Achellis Foundation; and Department of Veterans Affairs. Reprints or correspondence: Dr. Linda Andrus, Lindsley F. Kimball Research Institute of the New York Blood Center, 310 E. 67th St., New York, NY 10021 ([email protected]).
PY - 1998
Y1 - 1998
N2 - 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-1(LAI) 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.
AB - 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-1(LAI) 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.
UR - http://www.scopus.com/inward/record.url?scp=0031968725&partnerID=8YFLogxK
U2 - 10.1086/515251
DO - 10.1086/515251
M3 - Article
C2 - 9534960
AN - SCOPUS:0031968725
SN - 0022-1899
VL - 177
SP - 889
EP - 897
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -