title: Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.
abstract: Broadly neutralizing antibodies (bNAbs), which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, we have examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and have selected donors for monoclonal antibody (mAb) generation. We then used a high-throughput neutralization screen of antibody-containing culture supernatants from about 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent mAbs that target a broadly neutralizing epitope. This epitope is preferentially expressed on trimeric Envelope protein and spans conserved regions of variable loops of the gp120 subunit. The results provide a framework for the design of new vaccine candidates for the elicitation of bNAb responses.
authors.affiliation: Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Walker
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Phogat
authors.forename: Po-Ying
authors.initials: PY
authors.lastname: Chan-Hui
authors.forename: Denise
authors.initials: D
authors.lastname: Wagner
authors.forename: Pham
authors.initials: P
authors.lastname: Phung
authors.forename: Julie L
authors.initials: JL
authors.lastname: Goss
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Simek
authors.forename: Steven
authors.initials: S
authors.lastname: Fling
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Mitcham
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Lehrman
authors.forename: Frances H
authors.initials: FH
authors.lastname: Priddy
authors.forename: Ole A
authors.initials: OA
authors.lastname: Olsen
authors.forename: Steven M
authors.initials: SM
authors.lastname: Frey
authors.forename: Phillip W
authors.initials: PW
authors.lastname: Hammond
authors.forename: Stephen
authors.initials: S
authors.lastname: Kaminsky
authors.forename: Timothy
authors.initials: T
authors.lastname: Zamb
authors.forename: Matthew
authors.initials: M
authors.lastname: Moyle
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Koff
authors.forename: Pascal
authors.initials: P
authors.lastname: Poignard
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D017954:Africa South of the Sahara; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011994:Recombinant Proteins; C514793:gp120 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1