Antibodies to C-C chemokine receptor 5 in normal human IgG block infection of 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 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.
Bouhlal
H
H
Institut National de la Santé et de la Recherche Médicale Unité II 430 and Université Pierre et Marie Curie, Hôpital Broussais, Paris, France.
Hocini
H
H
Quillent-Grégoire
C
C
Donkova
V
V
Rose
S
S
Amara
A
A
Longhi
R
R
Haeffner-Cavaillon
N
N
Beretta
A
A
Kaveri
S V
SV
Kazatchkine
M D
MD
D000818:Animals; D019380:Anti-HIV Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D000906:Antibodies / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D001666:Binding Sites, Antibody / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006224:Cricetinae; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology*; D016756:Immunoglobulins, Intravenous / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D008214:Lymphocytes / Q000276:immunology / Q000821:virology*; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism
D019380:Anti-HIV Agents; D000906:Antibodies; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D019713:Receptors, CCR5