Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-HIV Agents / isolation & purification
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Anti-HIV Agents / metabolism
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Anti-HIV Agents / pharmacology*
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Antibodies / isolation & purification
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Antibodies / metabolism
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Antibodies / pharmacology*
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Binding Sites, Antibody / immunology
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Binding, Competitive / immunology
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CCR5 Receptor Antagonists
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CHO Cells
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Cells, Cultured
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Chemokine CCL5 / antagonists & inhibitors
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Chemokine CCL5 / metabolism
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Cricetinae
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HIV-1 / immunology*
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HeLa Cells
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Humans
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Immunoglobulin G / metabolism
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Immunoglobulin G / pharmacology*
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Immunoglobulins, Intravenous / metabolism
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Immunosuppressive Agents / isolation & purification
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Immunosuppressive Agents / metabolism
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Immunosuppressive Agents / pharmacology*
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Lymphocytes / immunology
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Lymphocytes / virology*
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Macrophages / immunology
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Macrophages / virology*
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Receptors, CCR5 / biosynthesis
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Receptors, CCR5 / immunology*
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Receptors, CCR5 / metabolism
Substances
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Anti-HIV Agents
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Antibodies
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CCR5 Receptor Antagonists
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Chemokine CCL5
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Immunoglobulin G
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Immunoglobulins, Intravenous
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Immunosuppressive Agents
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Receptors, CCR5