The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat

Significance Despite decades of research, an effective HIV-1 vaccine remains elusive. One potential vaccine target is the N-heptad repeat (NHR) region of gp41, which is the target of the FDA-approved drug enfuvirtide. However, monoclonal antibodies and antisera targeting this region have only been modestly neutralizing to date. Here, we show that the neutralization potency of the well-characterized anti-NHR antibody D5 is increased >5,000-fold by expression of FcγRI (CD64) on cells. Since FcγRI is expressed on macrophages and dendritic cells, which are implicated in the early establishment of HIV-1 infection following sexual transmission, these results may be important to HIV-1 vaccine development.