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 Fc␥Rs present on macrophages and iDC. We propose that, if such nonneutralizing inhibitory antibodies limit mucosal HIV transmission, they should be induced by vaccination.

The Neutralization Properties of a HIV-Specific Antibody Are Markedly Altered by Glycosylation Events Outside the Antigen-Binding Domain

“…In this report we describe the acquired capacity of the human F240 mAb to the immunodominant region of gp41 to neutralize infection in a traditional neutralization assay when it is generated as a recombinant Ab and expressed in CHO cells. It is worth noting that although the F240 Ab has been previously characterized as nonneutralizing, a recent report has shown that this Ab (and other nonneutralizing Abs) is capable of inhibiting viral replication by mechanisms distinct from those mediated on the virion surface by the Ab Agbinding regions (45).…”

Recombinant gp120 Vaccine-Induced Antibodies Inhibit Clinical Strains of HIV-1 in the Presence of Fc Receptor-Bearing Effector Cells and Correlate Inversely with HIV Infection Rate

“…This interaction results in reduced virus yield due to target cell death from Ab-dependent cellular cytotoxicity (ADCC), triggering of soluble antiviral factors, or Fc␥R-mediated phagocytosis of immune complexes (11,12). ADCVI Ab is measurable early during acute HIV infection and correlates inversely with plasma viral load (11).…”

Les anticorps anti-VIH

“…Des anticorps dépourvus d'activité neutralisante, mais exerçant une activité inhibitrice, ont été identifiés [12]. L'activité anti-VIH de ces anticorps, dénommés anticorps non neutralisants inhibiteurs (AcNoNI), est strictement dépendante de la liaison entre leur région Fc et un récepteur Fc exprimé à la surface d'une cellule effectrice.…”

“…Ils reconnaissent des épitopes spécifiques de la gp120 ou de [12,13] (Figure 3). En effet, lorsque des cellules présentatrices d'antigène (cellules dendritiques [DC] ou macrophages), qui expriment les récepteurs au Fc de type γ (RFcγ), sont les cibles du VIH plutôt que des lymphocytes T CD4 (dépourvus de RFcγ), l'activité inhibitrice des IgG est augmentée de façon drastique (100 à 1 000 fois pour les DC ou les macrophages, respectivement [13,14]).…”