RECOMBINANT HUMAN MONOCLONAL-ANTIBODY IGG1B12 NEUTRALIZES DIVERSE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PRIMARY ISOLATES

The CD4-binding domain of human immunodeficiency virus type 1 (HIV-1) gp120 elicits antibodies that are present in infected human sera, Mono clonal antibodies that recognize the HIV-1 gp120 CD4-binding domain ha ve been isolated, Some of these antibodies can neutralize laboratory-a dapted strains of HIV-1 and probably mediate neutralization by interfe ring with virus binding to its cellular CD4 receptor, However, most an ti-CD4 binding domain antibodies do not neutralize primary HIV-1 isola tes, We used primary HIV-1 isolates in an infectivity reduction assay to test the uniquely derived anti-CD4 binding domain recombinant human monoclonal antibody, IgG1b12. All of the tested HIV-1 isolates were n eutralized by this antibody, Additional studies indicated that neutral ization of a primary isolate with MAb IgG1b12 did not require continuo us exposure of human peripheral blood mononuclear cell cultures to the antibody, Finally, a complete IgG(1) molecule of an in vitro-selected b12 FAb mutant with a >400-fold increase in affinity was assembled, e xpressed in mammalian cells, and evaluated in the infectivity reductio n assay in comparative studies with the parent IgG1b12 antibody, The m utant did not retain the level of primary isolate neutralization poten cy that was a property of the parent molecule, Thus, we confirm that r ecombinant IgG1b12 has a unique specificity, and that it can neutraliz e all primary isolates tested in human PBMC cultures in vitro.