Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection

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 immunizatio...

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Vydané v:Journal of virology Ročník 82; číslo 1; s. 115
Hlavní autori: Alam, S Munir, Scearce, Richard M, Parks, Robert J, Plonk, Kelly, Plonk, Steven G, Sutherland, Laura L, Gorny, Miroslaw K, Zolla-Pazner, Susan, Vanleeuwen, Stacie, Moody, M Anthony, Xia, Shi-Mao, Montefiori, David C, Tomaras, Georgia D, Weinhold, Kent J, Karim, Salim Abdool, Hicks, Charles B, Liao, Hua-Xin, Robinson, James, Shaw, George M, Haynes, Barton F
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.01.2008
Predmet:
Animals
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - isolation & purification
Cross Reactions
Epitopes - immunology
HIV Antibodies - blood
HIV Antibodies - immunology
HIV Antibodies - metabolism
HIV Envelope Protein gp41 - immunology
HIV Infections - immunology
HIV-1 - immunology
Humans
Kinetics
Lipids - immunology
Mice
Neutralization Tests
Protein Binding
ISSN:1098-5514, 1098-5514
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1098-5514
1098-5514
DOI:10.1128/JVI.00927-07