title: Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1.
abstract: Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xueling
authors.initials: X
authors.lastname: Wu
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Li
authors.forename: Carl-Magnus
authors.initials: CM
authors.lastname: Hogerkorp
authors.forename: William R
authors.initials: WR
authors.lastname: Schief
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Tongqing
authors.initials: T
authors.lastname: Zhou
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schmidt
authors.forename: Lan
authors.initials: L
authors.lastname: Wu
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Longo
authors.forename: Krisha
authors.initials: K
authors.lastname: McKee
authors.forename: Sijy
authors.initials: S
authors.lastname: O'Dell
authors.forename: Mark K
authors.initials: MK
authors.lastname: Louder
authors.forename: Diane L
authors.initials: DL
authors.lastname: Wycuff
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.forename: Martha
authors.initials: M
authors.lastname: Nason
authors.forename: Nicole
authors.initials: N
authors.lastname: Doria-Rose
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wyatt
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
mesh_terms: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D050438:Genes, Immunoglobulin Heavy Chain; D050439:Genes, Immunoglobulin Light Chain; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins