Bispecific antibody targeting of human immunodeficiency virus type 1 (HIV-1) glycoprotein 41 to human macrophages through the Fc IgG receptor I mediates neutralizing effects in HIV-1 infection.
Human monocyte-derived macrophages that express the CD4 molecule and the Fc receptor for IgG (Fc gamma R) play a major role in the pathogenesis of human immunodeficiency virus (HIV) infection. To explore this possibility further, human monoclonal antibody to glycoprotein 41 (gp41) was produced, and a heterobifunctional antibody composed of F(ab') x F(ab')2 fragments of monoclonal anti-gp41 and anti-Fc gamma RI 22.2 were constructed. Both antibodies were analyzed for neutralizing effects, and the role of the CD4 molecule in HIV infection was studied with human monocyte-derived macrophages. The bispecific antibody exhibited strong neutralizing properties, in contrast to the monoclonal anti-gp41 antibody. Moreover, in the presence of monoclonal anti-Leu-3a antibody, viral production was completely inhibited. These findings demonstrate the necessity of the CD4 molecule in HIV infection of human macrophages and emphasize the usefulness of such heterobifunctional antibody directed to virus and monocyte-derived macrophage Fc receptors in prevention of HIV infection.
Mabondzo
A
A
Laboratoire de Neuropathologie Expérimentale et Neurovirologie, Service de Santé des Armées, Commissariat à l'Energie Atomique, Fontenay aux Roses, France.
Aussage
P
P
Bartholeyns
J
J
Le Naour
R
R
Raoul
H
H
Romet-Lemonne
J L
JL
Dormont
D
D
D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D000943:Antigens, Differentiation / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D015700:HIV Envelope Protein gp41; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG