A human monoclonal antibody against the CD4-binding site of HIV1 gp120 exhibits potent, broadly neutralizing activity.
A human monoclonal antibody (HuMAb) against HIV1, 1125H, was isolated from an asymptomatic, seropositive haemophiliac. This antibody was specific for gp120, and its binding to gp120 was inhibited by soluble CD4, indicating that its epitope was in or near the CD4-binding site. 1125H antibody recognized a variety of divergent HIV1 strains, including most laboratory strains tested as well as some early passage isolates. Commensurate with its specificity and high apparent affinity, 1125H exhibited potent neutralizing activity against IIIB, MN, RF and SF-2 strains. The epitope recognized by 1125H was destroyed by reduction of disulphide bonds, but not by removal of N-linked sugars. Thus, the epitope was conformationally determined and did not involve carbohydrate. Data from radioimmunoprecipitation/SDS-PAGE analysis of proteolytically cleaved viral lysate further indicated that the epitope of 1125H was not affected by cleavage at the V3 loop of gp120, provided that gp120 disulphide bonds remained intact. The potential use of HuMAb 1125H in passive immunotherapy against HIV is discussed as well as the importance of including its epitope in an AIDS vaccine.
Tilley
S A
SA
Public Health Research Institute, New York, NY 10016.
Honnen
W J
WJ
Racho
M E
ME
Hilgartner
M
M
Pinter
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001665:Binding Sites; D015704:CD4 Antigens / Q000276:immunology*; D004220:Disulfides; D000939:Epitopes / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006467:Hemophilia A / Q000276:immunology; D006801:Humans; D009500:Neutralization Tests; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D004220:Disulfides; D000939:Epitopes; D015699:HIV Envelope Protein gp120