title: Broad neutralization coverage of HIV by multiple highly potent antibodies.
abstract: Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine.
authors.affiliation: Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Walker
authors.forename: Michael
authors.initials: M
authors.lastname: Huber
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Doores
authors.forename: Emilia
authors.initials: E
authors.lastname: Falkowska
authors.forename: Robert
authors.initials: R
authors.lastname: Pejchal
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Julien
authors.forename: Sheng-Kai
authors.initials: SK
authors.lastname: Wang
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramos
authors.forename: Po-Ying
authors.initials: PY
authors.lastname: Chan-Hui
authors.forename: Matthew
authors.initials: M
authors.lastname: Moyle
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Mitcham
authors.forename: Phillip W
authors.initials: PW
authors.lastname: Hammond
authors.forename: Ole A
authors.initials: OA
authors.lastname: Olsen
authors.forename: Pham
authors.initials: P
authors.lastname: Phung
authors.forename: Steven
authors.initials: S
authors.lastname: Fling
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: Sanjay
authors.initials: S
authors.lastname: Phogat
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Simek
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Koff
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Pascal
authors.initials: P
authors.lastname: Poignard
mesh_terms: D016915:AIDS Vaccines / Q000096:biosynthesis / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002460:Cell Line; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D006031:Glycosylation; D057809:HEK293 Cells; D006678:HIV / Q000145:classification* / Q000276:immunology* / Q000302:isolation & purification; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000097:blood / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D006023:Glycoproteins; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins; D007106:Immune Sera