Abstract
A chimeric mouse–human antibody (Cβ1) was constructed that recognized the principal neutralizing domain (PND) of human immunodeficiency virus type 1 (HIV-1) gp120. The constant (C) immunoglobulin regions (C-γ1 and Cκ) of a mouse monoclonal antibody, 0.5β, were substituted for the human Cγ1 and Cκ by recombining the DNA modules encoding variable or C regions. The DNA constructs were then transfected into X63 Ag8.653 myeloma cells. A clone with a high production of the chimeric antibody (Cβ1) was selected. This antibody was tested for its biological activity against HIV-1. It bound to the surface of HTLV-IIIB-infected cells and reacted with gp120/160 with equal affinity and specificity to that of the parental 0.5β murine monoclonal antibody in a Western blot assay. Neutralization and/or enhancement of HIV infection were evaluated with Cβ1 and 0.5β. Both Cβ1 and 0.5β neutralized cell-to-cell infection and cell-free virus infection by HTLV-IIIB. Antibody-dependence enhancement of HIV infection was not observed with either Cβ1 or 0.5β in the presence or absence of human complement. Antibody-dependent cell-mediated cytolysis (ADCC) and antibody-dependent complement-mediated cytolysis (ACC) were observed with Cβ1 but not with the parental 0.5β. These findings suggest that the neutralizing antibodies to PND may neutralize but not enhance HIV infection. Furthermore, the high levels of ACC and ADCC shown against HIV-infected cells by Cβ1 indicate that the clinical application of such monoclonal antibodies may be possible.
Get full access to this article
View all access options for this article.