Abstract
Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. We report that four human anti-phospholipid monoclonal antibodies (mAbs) (PGN632, P1, IS4, and CL1) inhibit HIV-1 CCR5-tropic (R5) primary isolate infection of peripheral blood mononuclear cells (PBMCs) with 80% inhibitory concentrations of <0.02 to approximately 10 microg/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1alpha and MIP-1beta. The release of these beta-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antibodies, Antiphospholipid / genetics
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Antibodies, Antiphospholipid / immunology
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Antibodies, Antiphospholipid / pharmacology*
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology*
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / virology
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Cardiolipins / immunology
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Cell Fusion
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Chemokine CCL3 / immunology
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Chemokine CCL3 / metabolism
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Chemokine CCL4 / immunology
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Chemokine CCL4 / metabolism
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Chemokines / metabolism
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Chemokines, CC / metabolism*
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Complementarity Determining Regions / genetics
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Culture Media, Conditioned / pharmacology
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Endotoxins / pharmacology
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Epithelial Cells / virology
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Giant Cells / cytology
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HIV-1 / classification
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HIV-1 / physiology*
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Humans
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Immunity, Innate / drug effects
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Immunity, Innate / immunology
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Immunoglobulin Fab Fragments / genetics
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Immunoglobulin Fab Fragments / immunology
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Immunoglobulin Fc Fragments / immunology
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Kinetics
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / virology
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Monocytes / drug effects
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Monocytes / immunology
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Monocytes / metabolism
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Monocytes / virology
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Mutation / genetics
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Mutation / immunology
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Phosphatidylethanolamines / immunology
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Phosphatidylserines / immunology
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Receptors, CCR5 / physiology*
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Viral Tropism / physiology*
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Virus Internalization / drug effects*
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beta 2-Glycoprotein I / immunology
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env Gene Products, Human Immunodeficiency Virus / immunology
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env Gene Products, Human Immunodeficiency Virus / metabolism
Substances
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1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine
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Antibodies, Antiphospholipid
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Antibodies, Monoclonal
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CCL3 protein, human
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CCL4 protein, human
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Cardiolipins
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Chemokine CCL3
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Chemokine CCL4
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Chemokines
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Chemokines, CC
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Complementarity Determining Regions
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Culture Media, Conditioned
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Endotoxins
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Immunoglobulin Fab Fragments
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Immunoglobulin Fc Fragments
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Phosphatidylethanolamines
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Phosphatidylserines
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Receptors, CCR5
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beta 2-Glycoprotein I
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env Gene Products, Human Immunodeficiency Virus