Human Immunodeficiency Virus Type 1 gp41 Antibodies That Mask Membrane Proximal Region Epitopes: Antibody Binding Kinetics, Induction, and Potential for Regulation in Acute Infection
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- S. Munir Alam
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Richard M. Scearce
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Robert J. Parks
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Kelly Plonk
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Steven G. Plonk
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Laura L. Sutherland
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Miroslaw K. Gorny
- New York University School of Medicine, New York, New York 15016
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- Susan Zolla-Pazner
- New York University School of Medicine, New York, New York 15016
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- Stacie VanLeeuwen
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- M. Anthony Moody
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Shi-Mao Xia
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- David C. Montefiori
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Georgia D. Tomaras
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Kent J. Weinhold
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Salim Abdool Karim
- University of KwaZulu-Natal, Durban, South Africa
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- Charles B. Hicks
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- Hua-Xin Liao
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
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- James Robinson
- Tulane University School of Medicine, New Orleans, Louisiana
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- George M. Shaw
- University of Alabama at Birmingham; Birmingham, Alabama 35294-0024
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- Barton F. Haynes
- Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School Medicine, Durham, North Carolina 27710
抄録
<jats:title>ABSTRACT</jats:title><jats:p>Two human monoclonal antibodies (MAbs) (2F5 and 4E10) against the human immunodeficiency virus type 1 (HIV-1) envelope g41 cluster II membrane proximal external region (MPER) broadly neutralize HIV-1 primary isolates. However, these antibody specificities are rare, are not induced by Env immunization or HIV-1 infection, and are polyspecific and also react with lipids such as cardiolipin or phosphatidylserine. To probe MPER anti-gp41 antibodies that are produced in HIV-1 infection, we have made two novel murine MAbs, 5A9 and 13H11, against HIV-1 gp41 envelope that partially cross-blocked 2F5 MAb binding to Env but did not neutralize HIV-1 primary isolates or bind host lipids. Competitive inhibition assays using labeled 13H11 MAb and HIV-1-positive patient plasma samples demonstrated that cluster II 13H11-blocking plasma antibodies were made in 83% of chronically HIV-1 infected patients and were acquired between 5 to 10 weeks after acute HIV-1 infection. Both the mouse 13H11 MAb and the three prototypic cluster II human MAbs (98-6, 126-6, and 167-D) blocked 2F5 binding to gp41 epitopes to variable degrees; the combination of 98-6 and 13H11 completely blocked 2F5 binding. These data provide support for the hypothesis that in some patients, B cells make nonneutralizing cluster II antibodies that may mask or otherwise down-modulate B-cell responses to immunogenic regions of gp41 that could be recognized by B cells capable of producing antibodies like 2F5.</jats:p>
収録刊行物
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- Journal of Virology
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Journal of Virology 82 (1), 115-125, 2008-01
American Society for Microbiology