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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AIDS Vaccines / immunology*
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Africa South of the Sahara
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Antibodies, Monoclonal / immunology*
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B-Lymphocyte Subsets / immunology
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Epitopes / immunology
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HIV Antibodies / biosynthesis
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HIV Antibodies / immunology*
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HIV Envelope Protein gp120 / chemistry
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HIV Envelope Protein gp120 / immunology*
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HIV Envelope Protein gp41 / immunology
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HIV Infections / immunology*
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HIV-1 / immunology*
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Humans
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Immunologic Memory
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Lymphocyte Activation
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Neutralization Tests
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Peptide Fragments / immunology
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Protein Multimerization
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Recombinant Proteins / immunology
Substances
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AIDS Vaccines
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Antibodies, Monoclonal
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Epitopes
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HIV Antibodies
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HIV Envelope Protein gp120
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HIV Envelope Protein gp41
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HIV envelope protein gp120 (305-321)
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Peptide Fragments
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Recombinant Proteins
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gp120 protein, Human immunodeficiency virus 1
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gp41 protein, Human immunodeficiency virus 1