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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.

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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  • Media type: E-Article
  • Title: Human Immunodeficiency Virus Type 1 gp41 Antibodies That Mask Membrane Proximal Region Epitopes: Antibody Binding Kinetics, Induction, and Potential for Regulation in Acute Infection
  • Contributor: 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.
  • imprint: American Society for Microbiology, 2008
  • Published in: Journal of Virology
  • Language: English
  • DOI: 10.1128/jvi.00927-07
  • ISSN: 0022-538X; 1098-5514
  • Keywords: Virology ; Insect Science ; Immunology ; Microbiology
  • Origination:
  • Footnote:
  • Description: <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>
  • Access State: Open Access