title: Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.
abstract: Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.
authors.affiliation: Duke University Human Vaccine Institute, Departments of Medicine and Immunology, Duke University School of Medicine, Durham, North Carolina 27710, USA. hliao@duke.edu
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authors.initials: HX
authors.lastname: Liao
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authors.lastname: Lynch
authors.forename: Tongqing
authors.initials: T
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: S Munir
authors.initials: SM
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authors.initials: KM
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authors.lastname: Kelsoe
authors.forename: Guang
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authors.lastname: Yang
authors.forename: Shi-Mao
authors.initials: SM
authors.lastname: Xia
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.forename: Krissey E
authors.initials: KE
authors.lastname: Lloyd
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Soderberg
authors.forename: Myron
authors.initials: M
authors.lastname: Cohen
authors.forename: Gift
authors.initials: G
authors.lastname: Kamanga
authors.forename: Mark K
authors.initials: MK
authors.lastname: Louder
authors.forename: Lillian M
authors.initials: LM
authors.lastname: Tran
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Fangping
authors.initials: F
authors.lastname: Cai
authors.forename: Sheri
authors.initials: S
authors.lastname: Chen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moquin
authors.forename: Xiulian
authors.initials: X
authors.lastname: Du
authors.forename: M Gordon
authors.initials: MG
authors.lastname: Joyce
authors.forename: Sanjay
authors.initials: S
authors.lastname: Srivatsan
authors.forename: Baoshan
authors.initials: B
authors.lastname: Zhang
authors.forename: Anqi
authors.initials: A
authors.lastname: Zheng
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.forename: Bette T M
authors.initials: BT
authors.lastname: Korber
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000349:Africa; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology; D019070:Cell Lineage; D002478:Cells, Cultured; D002999:Clone Cells / Q000166:cytology; D003429:Cross Reactions / Q000276:immunology; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D019143:Evolution, Molecular; D015483:HIV Antibodies / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry* / Q000145:classification / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D010802:Phylogeny; D017434:Protein Structure, Tertiary
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120
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