title: Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein.
abstract: Two to three years after infection, a fraction of HIV-1-infected individuals develop serologic activity that neutralizes most viral isolates. Broadly neutralizing antibodies that recognize the HIV-1 envelope protein have been isolated from these patients by single-cell sorting and by neutralization screens. Here, we report a new method for anti-HIV-1 antibody isolation based on capturing single B cells that recognize the HIV-1 envelope protein expressed on the surface of transfected cells. Although far less efficient than soluble protein baits, the cell-based capture method identified antibodies that bind to a new broadly neutralizing epitope in the vicinity of the V3 loop and the CD4-induced site (CD4i). The new epitope is expressed on the cell surface form of the HIV-1 spike, but not on soluble forms of the same envelope protein. Moreover, the new antibodies complement the neutralization spectrum of potent broadly neutralizing anti-CD4 binding site (CD4bs) antibodies obtained from the same individual. Thus, combinations of potent broadly neutralizing antibodies with complementary activity can account for the breadth and potency of naturally arising anti-HIV-1 serologic activity. Therefore, vaccines aimed at eliciting anti-HIV-1 serologic breadth and potency should not be limited to single epitopes.
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors: Florian
authors: F
authors: Klein
authors: Christian
authors: C
authors: Gaebler
authors: Hugo
authors: H
authors: Mouquet
authors: D Noah
authors: DN
authors: Sather
authors: Clara
authors: C
authors: Lehmann
authors: Johannes F
authors: JF
authors: Scheid
authors: Zane
authors: Z
authors: Kraft
authors: Yan
authors: Y
authors: Liu
authors: John
authors: J
authors: Pietzsch
authors: Arlene
authors: A
authors: Hurley
authors: Pascal
authors: P
authors: Poignard
authors: Ten
authors: T
authors: Feizi
authors: Lynn
authors: L
authors: Morris
authors: Bruce D
authors: BD
authors: Walker
authors: Gerd
authors: G
authors: Fätkenheuer
authors: Michael S
authors: MS
authors: Seaman
authors: Leonidas
authors: L
authors: Stamatatos
authors: Michel C
authors: MC
authors: Nussenzweig
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160