TARGETING HIV-1 TO FC-GAMMA-R ON HUMAN PHAGOCYTES VIA BISPECIFIC ANTIBODIES REDUCES INFECTIVITY OF HIV-1 TO T-CELLS

In addition to CD4, the primary receptor to which the human immunodefi ciency virus type 1 (HIV-1) binds, mononuclear phagocytes (monocytes) express three classes of Fc receptors for immunoglobulin G (Fc gamma R ). We have previously shown that infection of monocytes by HIV-1 is in hibited when bispecific antibodies (BsAbs) are used to target the viru s to either the type I, type II, or type III Fc gamma R on these cells . Infection of monocytes was not inhibited when HIV-1 was targeted to either human leukocyte antigen class I or CD33. We have extended these studies to examine the ability of BsAbs plus polymorphonuclear leukoc ytes (neutrophils, PMNs) and monocytes to reduce infectivity of HIV-1 to cells from the human T cell lymphoma line, H9. The production of HI V-1 following interaction of virus with BsAb and phagocytes was determ ined in an indicator cell assay by mixing BsAb, HIV-1, and phagocytes with uninfected H9 cells. Productive infection of H9 cells was quantit ated on subsequent days by measuring p24 gag antigen levels in superna tants by enzyme-linked immunosorbent assay. Our findings show that the addition of interferon-alpha-activated PMNs or monocytes to cultures of HIV-1 plus H9 cells in the absence of BsAb results in a marked redu ction in p24: levels equivalent to 85 to 90% of control levels. With t he combination of BsAb (anti-Fc gamma RI x anti-gp120) plus IFN-gamma- activated phagocytes, levels of p24 in H9 cultures were below those at culture initiation. These findings demonstrate that IFN-gamma-activat ed phagocytes can affect the natural course of HIV-1 infection of T ce lls, a finding of potential clinical importance.