IMMUNOBIOLOGY Neutralizing antibodies inhibit HIV-1 transfer from primary dendritic cells to

Dendritic cells (DCs) support only low levels of HIV-1 replication, but have been shown to transfer infectious viral par-ticles highly efficiently to neighboring permissive CD4 T lymphocytes. This mode of cell-to-cell HIV-1 spread may be a predominant mode of infection and dis-semination. In the present study, we ana-lyzed the kinetics of fusion, replication, and the ability of HIV-1–specific Abs to inhibit HIV-1 transfer from immature DCs to autologous CD4 T lymphocytes. We found that neutralizing mAbs prevented HIV-1 transfer to CD4 T lymphocytes in trans and in cis, whereas nonneutralizing Abs did not. Neutralizing Abs also signifi-cantly decreased HIV-1 replication in DCs, even when added 2 hours after HIV-1 infection. Interestingly, a similar inhibi-tion of HIV-1 replication in DCs was de-tected with some nonneutralizing Abs and was correlated with DC maturation. We suggest that the binding of HIV-1-specific Abs to FcRs leads to HIV-1 inhibition in DCs by triggering DC matura-tion. This efficient inhibition of HIV-1 trans-fer by Abs highlights the importance of inducing HIV-specific Abs by vaccination directly at the mucosal portal of HIV-1 entry to prevent early dissemination after sexual transmission. (Blood. 2012;120(18): 3708-3717