title: A broad range of mutations in HIV-1 neutralizing human monoclonal antibodies specific for V2, V3, and the CD4 binding site.
abstract: The HIV vaccine-induced neutralizing antibodies (Abs) display low rates of mutation in their variable regions. To determine the range of neutralization mediated by similar human monoclonal Abs (mAbs) but derived from unselected chronically HIV-1 infected subjects, we tested a panel of 66 mAbs specific to V3, CD4 binding site (CD4bs) and V2 regions. The mAbs were tested against 41 pseudoviruses, including 15 tier 1 and 26 tier 2, 3 viruses, showing that the neutralization potency and breadth of anti-V3 mAbs were significantly higher than those of the anti-CD4bs and anti-V2 mAbs, and only anti-V3 mAbs were able to neutralize some tier 2, 3 viruses. The percentage of mutations in the variable regions of the heavy (VH) and light (VL) chains varied broadly in a range from 2% to 18% and correlated moderately with the neutralization breadth of tier 2, 3 viruses. There was no correlation with neutralization of tier 1 viruses as some mAbs with low and high percentages of mutations neutralized the same number of viruses. The electrostatic interactions between anti-V3 mAbs and the charged V3 region may contribute to their neutralization because the isoelectric points of the VH CDR3 of 48 anti-V3 mAbs were inversely correlated with the neutralization breadth of tier 2, 3 viruses. The results demonstrate that infection-induced antibodies to CD4bs, V3 and V2 regions can mediate cross-clade neutralization despite low levels of mutations which can be achieved by HIV-1 vaccine-induced antibodies.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Liuzhe
authors.initials: L
authors.lastname: Li
authors.affiliation: Veterans Affairs Medical Center, New York, NY 10010, USA.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Constance
authors.initials: C
authors.lastname: Williams
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Volsky
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Steczko
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Luthra
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Phillipe
authors.initials: P
authors.lastname: Nyambi
authors.affiliation: Institute of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Nadas
authors.affiliation: IMGT(®), The International ImMunoGeneTics Information System(®), CNRS, Montpellier University, Montpellier, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Giudicelli
authors.affiliation: IMGT(®), The International ImMunoGeneTics Information System(®), CNRS, Montpellier University, Montpellier, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Lefranc
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Veterans Affairs Medical Center, New York, NY 10010, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: mirek.gorny@nyumc.org.
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
mesh_terms: D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000737:chemistry / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D011485:Protein Binding
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007135:Immunoglobulin Variable Region; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: CD4 binding site; HIV neutralizing antibodies; HIV-1; Human monoclonal antibodies; Somatic mutation; V2 region; V3 region