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*
Institut National de la Santé et de la Recherche Médicale Unité II 430 and Université Pierre et Marie Curie, Hôpital Broussais, Paris, France;
Centre Integré de Recherches Biocliniques sur le SIDA (CIRBS), Hôpital St. Joseph, Paris, France;
Institut Pasteur, Paris, France;
Fondazione Centro S. Raffaele Del Monte Tabor, Milan, Italy; and
¶
Consiglio Nazionale delle Ricerche (CNR) Laboratory, Milan, Italy.
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 consisting of a synthetic peptide corresponding to the N-terminus of CCR5 coupled to Sepharose. Natural anti-CCR5 Abs inhibited the binding of RANTES to macrophages, demonstrating their interaction with the coreceptor of R5-tropic HIV-1. Affinity-purified anti-CCR5 Ig further inhibited infection of lymphocytes and monocytes/macrophages with primary and laboratory-adapted strains 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 suitable for development of novel passive immunotherapy regimens in specific clinical settings in HIV infection.
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