Nonneutralizing antibodies are able to inhibit human immunodeficiency virus type 1 replication in macrophages and immature dendritic cells

Abstract

Only five monoclonal antibodies (MAbs) neutralizing a broad range of primary isolates (PI) have been identified up to now. We have found that some MAbs with no neutralizing activities according to the "conventional" neutralization assay, involving phytohemagglutinin-stimulated peripheral blood mononuclear cells as targets, efficiently inhibit the replication of human immunodeficiency virus type 1 (HIV-1) PI in macrophages and immature dendritic cells (iDC). The mechanism of inhibition is distinct from the neutralization of infectivity occurring via Fab fragments and involves the interaction of the F portion with the FcgammaRs present on macrophages and iDC. We propose that, if such nonneutralizing inhibitory antibodies limit mucosal HIV transmission, they should be induced by vaccination.

FIG. 1.

Inhibition of HIV replication by MAb 447-52D (whole IgG) or its corresponding Fab fragment in PHA-stimulated PBMC, macrophages, and iDC. Values correspond to the percentage of infected cells in the presence of different dilutions of 447-52D versus infected cells without Ab (control infected cells). Mean and standard deviation of two independent wells obtained for one representative experiment are shown.

FIG. 2.

Involvement of MAb 240-D paratope and Fc domains in its inhibitory activity of HIV replication in macrophages. (A) FcγRs were blocked by the addition of 10 μg of anti-FcγRI (CD64), anti-FcγRII (CD32), or anti-FcγRIII (CD16) to macrophages for 30 min before the addition of the virus-MAb 240 mixture using the conditions of the neutralization assay. (B) Competition experiments were performed by mixing, in conditions of neutralization assays, MAb 240-D and Bx08 with peptide PID (gp41, aa 593 to 616) at 25 μg/ml or rgp160ΔPID at 12.5 μg/ml. Then, 1 h later, the mixture was added to macrophages. The percentages of infected cells were determined by flow cytometry.