title: Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce beta-chemokines.
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.
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. moody007@mc.duke.edu
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.forename: M Kelly
authors.initials: MK
authors.lastname: Plonk
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Kozink
authors.forename: Mark S
authors.initials: MS
authors.lastname: Drinker
authors.forename: Ruijun
authors.initials: R
authors.lastname: Zhang
authors.forename: Shi-Mao
authors.initials: SM
authors.lastname: Xia
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Ian P
authors.initials: IP
authors.lastname: Giles
authors.forename: John C
authors.initials: JC
authors.lastname: Kappes
authors.forename: Christina
authors.initials: C
authors.lastname: Ochsenbauer-Jambor
authors.forename: Tara G
authors.initials: TG
authors.lastname: Edmonds
authors.forename: Melina
authors.initials: M
authors.lastname: Soares
authors.forename: Gustavo
authors.initials: G
authors.lastname: Barbero
authors.forename: Donald N
authors.initials: DN
authors.lastname: Forthal
authors.forename: Gary
authors.initials: G
authors.lastname: Landucci
authors.forename: Connie
authors.initials: C
authors.lastname: Chang
authors.forename: Steven W
authors.initials: SW
authors.lastname: King
authors.forename: Anita
authors.initials: A
authors.lastname: Kavlie
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Denny
authors.forename: Kwan-Ki
authors.initials: KK
authors.lastname: Hwang
authors.forename: Pojen P
authors.initials: PP
authors.lastname: Chen
authors.forename: Philip E
authors.initials: PE
authors.lastname: Thorpe
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D002308:Cardiolipins / Q000276:immunology; D002459:Cell Fusion; D054405:Chemokine CCL3 / Q000276:immunology / Q000378:metabolism; D054407:Chemokine CCL4 / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism*; D022801:Complementarity Determining Regions / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D004847:Epithelial Cells / Q000821:virology; D015726:Giant Cells / Q000166:cytology; D015497:HIV-1 / Q000145:classification / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009154:Mutation / Q000235:genetics / Q000276:immunology; D010714:Phosphatidylethanolamines / Q000276:immunology; D010718:Phosphatidylserines / Q000276:immunology; D019713:Receptors, CCR5 / Q000502:physiology*; D056189:Viral Tropism / Q000502:physiology*; D053586:Virus Internalization / Q000187:drug effects*; D053482:beta 2-Glycoprotein I / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; C515429:CCL3 protein, human; C066507:CCL4 protein, human; D002308:Cardiolipins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019742:Chemokines, CC; D022801:Complementarity Determining Regions; D017077:Culture Media, Conditioned; D004731:Endotoxins; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D019713:Receptors, CCR5; D053482:beta 2-Glycoprotein I; D054299:env Gene Products, Human Immunodeficiency Virus