title: Memory B cell antibodies to HIV-1 gp140 cloned from individuals infected with clade A and B viruses.
abstract: Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is a crucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important as these antibodies may target conserved epitopes on the HIV envelope gp160 protein. To this end we have used a clade B YU-2 gp140 trimeric antigen and single-cell antibody cloning methods to obtain 189 new anti-gp140 antibodies representing 51 independent B cell clones from the IgG memory B cells of 3 patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing a diverse antibody response to HIV gp140 envelope protein, characterized by differentially expanded B-cell clones producing highly hypermutated antibodies with heterogenous gp140-specificity and neutralizing activity. In addition to their high-affinity binding to the HIV spike, the vast majority of the new anti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VRC01 or PG9, two clonally-related antibodies isolated from a clade A HIV-1 infected donor, directed against the gp120 variable loop 3, rank in the top 5% of the neutralizers identified in our large collection of 185 unique gp140-specific antibodies in terms of breadth and potency.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Scheid
authors.forename: Malte
authors.initials: M
authors.lastname: Warncke
authors.forename: John
authors.initials: J
authors.lastname: Pietzsch
authors.forename: Thiago Y K
authors.initials: TY
authors.lastname: Oliveira
authors.forename: Klara
authors.initials: K
authors.lastname: Velinzon
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000595:Amino Acid Sequence; D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1