Antibodies to C-C chemokine receptor 5 in normal human IgG block infectionof macrophages and lymphocytes with primary R5-tropic strains of HIV-1

In the present study, we demonstrate that normal human IgG for therapeutic use (i.v. Ig) contains natural Abs directed against the CCR5 coreceptor for HIV-1. Abs to CCR5 were isolated from i.v. Ig using an affinity matrix con sisting of a synthetic peptide corresponding to the N-terminus of CCR5 coup led to Sepharose. Natural anti-CCR5 Abs inhibited the binding of RANTES to macrophages, demonstrating their interaction with the coreceptor of R5-trop ic HIV-1. Affinity-purified anti-CCR5 Ig further inhibited infection of lym phocytes and monocytes/macrophages with primary and laboratory-adapted stra ins of HIV-1, but did not inhibit infection with X4-tropic HIV. Our results suggest that anti-CCR5 Abs from healthy immunocompetent donors may be suit able for development of novel passive immunotherapy regimens in specific cl inical settings in HIV infection.