Conformational changes in env oligomer induced by an antibody dependent on the V3 loop base.
OBJECTIVE
The HIV-1 env oligomer is structured such that conserved, neutralizing epitopes are obscured by gp120 variable loops. We have studied the ability of an IgG2 human monoclonal antibody (hmAb), F425 B4e8 (B4e8), dependent upon the base of the V3 loop, to induce conformational changes in the env oligomer.


METHODS
The effect of B4e8 antibody on the exposure of neutralizing epitopes and viral neutralization was studied in combination with other hmAb.


METHODS
Epitope exposure and viral neutralization was determined using native, intact primary isolate virions.


RESULTS
B4e8 antibody neutralizes infection and binds to HIV-infected cells and primary isolate virions. B4e8 and 2G12 enhanced the binding of each other to infected cells or virus and the combination resulted in synergistic neutralization. B4e8 also enhanced the binding of CD4i and CD4 binding site antibodies.


CONCLUSIONS
The conserved epitopes exposed by B4e8 are similar to those exposed by the movement of the variable loops following CD4 engagement. Further studies with select antibody combinations should provide important information for the design of effective immunotherapeutic agents.
Cavacini
Lisa
L
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Duval
Mark
M
Song
Leslie
L
Sangster
Rebecca
R
Xiang
Shi-hua
SH
Sodroski
Joseph
J
Posner
Marshall
M
D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology*; D011487:Protein Conformation; D014771:Virion / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007074:Immunoglobulin G; D010446:Peptide Fragments