Effect of antibody valency on interaction with cell-surface expressed HIV-1 and viral neutralization.
F(ab) and F(ab')2 fragments of the human mAb, F105, were compared to intact IgG1 for binding to the CD4 binding site of HIV-1/gp120 on the surface of infected cells and viral neutralization. F105 IgG1 and F(ab')2 bound to IIIB, MN, and RF infected cells and neutralized these strains in an identical fashion, whereas strain-specific differences were observed in F(ab) activity. Although F105 F(ab) bound with equivalent affinity to IIIB-infected cells, there was a 4- to 10-fold decrease in the neutralization of IIIB by monovalent F(ab) compared to the bivalent molecules. F105 F(ab) demonstrated both diminished binding and neutralization of the MN strain and failed to bind or neutralize the RF strain. When cooperativity of V3 loop antibody (V3ab) with F105 IgG and fragments was examined, the binding of F105 IgG and F(ab')2 to IIIB-, MN-, or RF-infected cells was modestly enhanced by V3ab; viral neutralization was substantially enhanced by the combination of V3ab and F105 IgG and F(ab')2. The combination of F105 F(ab) with V3ab also resulted in significant cooperative neutralization of IIIB and MN, but the lack of F105 F(ab) binding and neutralization of RF was unaltered by V3ab. These results suggest that bivalent interaction may be important in binding and neutralization of virus, and support the notion that this interaction may depend on conformational changes in oligomeric gp120 on intact virions and cell surface rather than on affinity or steric effects.
Cavacini
L A
LA
Department of Medicine, New England Deaconess Hospital, Boston, MA 02215.
Emes
C L
CL
Power
J
J
Duval
M
M
Posner
M R
MR
D000911:Antibodies, Monoclonal; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000382:microbiology; D000939:Epitopes; D015483:HIV Antibodies / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D009500:Neutralization Tests; D015728:Receptors, HIV / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D015728:Receptors, HIV