Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1

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J. Virol., 02 1996, 1100-1108, Vol 70, No. 2
Copyright © 1996, American Society for Microbiology

Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1

A Trkola, M Purtscher, T Muster, C Ballaun, A Buchacher, N Sullivan, K Srinivasan, J Sodroski, JP Moore and H Katinger
Aaron Diamond AIDS Research Center, New York University School of Medicine, New York 10016, USA.

We have isolated and characterized human monoclonal antibody 2G12 to the gp120 surface glycoprotein of human immunodeficiency virus type 1 (HIV-1). This antibody potently and broadly neutralizes primary and T- cell line-adapted clade B strains of HIV-1 in a peripheral blood mononuclear cell-based assay and inhibits syncytium formation in the AA- 2 cell line. Furthermore, 2G12 possesses neutralizing activity against strains from clade A but not from clade E. Complement- and antibody- dependent cellular cytotoxicity-activating functions of 2G12 were also defined. The gp120 epitope recognized by 2G12 was found to be distinctive; binding of 2G12 to LAI recombinant gp120 was abolished by amino acid substitutions removing N-linked carbohydrates in the C2, C3, V4, and C4 regions of gp120. This gp120 mutant recognition pattern has not previously been observed, indicating that the 2G12 epitope is unusual. consistent with this, antibodies able to block 2G12 binding to recombinant gp120 were not detected in significant quantities in 16 HIV- positive human serum samples.

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Zhang, M.-Y., Xiao, X., Sidorov, I. A., Choudhry, V., Cham, F., Zhang, P. F., Bouma, P., Zwick, M., Choudhary, A., Montefiori, D. C., Broder, C. C., Burton, D. R., Quinnan, G. V. Jr., Dimitrov, D. S. (2004). Identification and Characterization of a New Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody. J. Virol. 78: 9233-9242 [Abstract] [Full Text]
Zhang, H., Huang, Y., Fayad, R., Spear, G. T., Qiao, L. (2004). Induction of Mucosal and Systemic Neutralizing Antibodies against Human Immunodeficiency Virus Type 1 (HIV-1) by Oral Immunization with Bovine Papillomavirus-HIV-1 gp41 Chimeric Virus-Like Particles. J. Virol. 78: 8342-8348 [Abstract] [Full Text]
Wang, W., Owen, S. M., Rudolph, D. L., Cole, A. M., Hong, T., Waring, A. J., Lal, R. B., Lehrer, R. I. (2004). Activity of {alpha}- and {theta}-Defensins against Primary Isolates of HIV-1. J. Immunol. 173: 515-520 [Abstract] [Full Text]
Haigwood, N. L., Montefiori, D. C., Sutton, W. F., McClure, J., Watson, A. J., Voss, G., Hirsch, V. M., Richardson, B. A., Letvin, N. L., Hu, S.-L., Johnson, P. R. (2004). Passive Immunotherapy in Simian Immunodeficiency Virus-Infected Macaques Accelerates the Development of Neutralizing Antibodies. J. Virol. 78: 5983-5995 [Abstract] [Full Text]
Pinter, A., Honnen, W. J., He, Y., Gorny, M. K., Zolla-Pazner, S., Kayman, S. C. (2004). The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol. 78: 5205-5215 [Abstract] [Full Text]
Madani, N., Perdigoto, A. L., Srinivasan, K., Cox, J. M., Chruma, J. J., LaLonde, J., Head, M., Smith, A. B. III, Sodroski, J. G. (2004). Localized Changes in the gp120 Envelope Glycoprotein Confer Resistance to Human Immunodeficiency Virus Entry Inhibitors BMS-806 and #155. J. Virol. 78: 3742-3752 [Abstract] [Full Text]
Lorin, C., Mollet, L., Delebecque, F., Combredet, C., Hurtrel, B., Charneau, P., Brahic, M., Tangy, F. (2004). A Single Injection of Recombinant Measles Virus Vaccines Expressing Human Immunodeficiency Virus (HIV) Type 1 Clade B Envelope Glycoproteins Induces Neutralizing Antibodies and Cellular Immune Responses to HIV. J. Virol. 78: 146-157 [Abstract] [Full Text]
Nabatov, A. A., Pollakis, G., Linnemann, T., Kliphius, A., Chalaby, M. I. M., Paxton, W. A. (2004). Intrapatient Alterations in the Human Immunodeficiency Virus Type 1 gp120 V1V2 and V3 Regions Differentially Modulate Coreceptor Usage, Virus Inhibition by CC/CXC Chemokines, Soluble CD4, and the b12 and 2G12 Monoclonal Antibodies. J. Virol. 78: 524-530 [Abstract] [Full Text]
Trkola, A., Kuster, H., Leemann, C., Ruprecht, C., Joos, B., Telenti, A., Hirschel, B., Weber, R., Bonhoeffer, S., Gunthard, H. F. (2003). Human Immunodeficiency Virus Type 1 Fitness Is a Determining Factor in Viral Rebound and Set Point in Chronic Infection. J. Virol. 77: 13146-13155 [Abstract] [Full Text]
Nishimura, Y., Igarashi, T., Haigwood, N. L., Sadjadpour, R., Donau, O. K., Buckler, C., Plishka, R. J., Buckler-White, A., Martin, M. A. (2003). Transfer of neutralizing IgG to macaques 6 h but not 24 h after SHIV infection confers sterilizing protection: Implications for HIV-1 vaccine development. Proc. Natl. Acad. Sci. USA 100: 15131-15136 [Abstract] [Full Text]
McKenna, P. M., Pomerantz, R. J., Dietzschold, B., McGettigan, J. P., Schnell, M. J. (2003). Covalently Linked Human Immunodeficiency Virus Type 1 gp120/gp41 Is Stably Anchored in Rhabdovirus Particles and Exposes Critical Neutralizing Epitopes. J. Virol. 77: 12782-12794 [Abstract] [Full Text]
Ohagen, A., Devitt, A., Kunstman, K. J., Gorry, P. R., Rose, P. P., Korber, B., Taylor, J., Levy, R., Murphy, R. L., Wolinsky, S. M., Gabuzda, D. (2003). Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1 env Genes Derived from Brain and Blood of Patients with AIDS. J. Virol. 77: 12336-12345 [Abstract] [Full Text]
Vermeire, K., Schols, D. (2003). Specific CD4 down-modulating compounds with potent anti-HIV activity. J. Leukoc. Biol. 74: 667-675 [Abstract] [Full Text]
Labrijn, A. F., Poignard, P., Raja, A., Zwick, M. B., Delgado, K., Franti, M., Binley, J., Vivona, V., Grundner, C., Huang, C.-C., Venturi, M., Petropoulos, C. J., Wrin, T., Dimitrov, D. S., Robinson, J., Kwong, P. D., Wyatt, R. T., Sodroski, J., Burton, D. R. (2003). Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1. J. Virol. 77: 10557-10565 [Abstract] [Full Text]
Painter, S. L., Biek, R., Holley, D. C., Poss, M. (2003). Envelope Variants from Women Recently Infected with Clade A Human Immunodeficiency Virus Type 1 Confer Distinct Phenotypes That Are Discerned by Competition and Neutralization Experiments. J. Virol. 77: 8448-8461 [Abstract] [Full Text]
Calarese, D. A., Scanlan, C. N., Zwick, M. B., Deechongkit, S., Mimura, Y., Kunert, R., Zhu, P., Wormald, M. R., Stanfield, R. L., Roux, K. H., Kelly, J. W., Rudd, P. M., Dwek, R. A., Katinger, H., Burton, D. R., Wilson, I. A. (2003). Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition. Science 300: 2065-2071 [Abstract] [Full Text]
Zwick, M. B., Kelleher, R., Jensen, R., Labrijn, A. F., Wang, M., Quinnan, G. V. Jr., Parren, P. W. H. I., Burton, D. R. (2003). A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol. 77: 6965-6978 [Abstract] [Full Text]
Louis, J. M., Nesheiwat, I., Chang, L., Clore, G. M., Bewley, C. A. (2003). Covalent Trimers of the Internal N-terminal Trimeric Coiled-coil of gp41 and Antibodies Directed against Them Are Potent Inhibitors of HIV Envelope-mediated Cell Fusion. J. Biol. Chem. 278: 20278-20285 [Abstract] [Full Text]
Zwick, M. B., Parren, P. W. H. I., Saphire, E. O., Church, S., Wang, M., Scott, J. K., Dawson, P. E., Wilson, I. A., Burton, D. R. (2003). Molecular Features of the Broadly Neutralizing Immunoglobulin G1 b12 Required for Recognition of Human Immunodeficiency Virus Type 1 gp120. J. Virol. 77: 5863-5876 [Abstract] [Full Text]
Pantophlet, R., Wilson, I. A., Burton, D. R. (2003). Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol. 77: 5889-5901 [Abstract] [Full Text]
Wolbank, S., Kunert, R., Stiegler, G., Katinger, H. (2003). Characterization of Human Class-Switched Polymeric (Immunoglobulin M [IgM] and IgA) Anti-Human Immunodeficiency Virus Type 1 Antibodies 2F5 and 2G12. J. Virol. 77: 4095-4103 [Abstract] [Full Text]
Stiegler, G., Katinger, H. (2003). Therapeutic potential of neutralizing antibodies in the treatment of HIV-1 infection. J Antimicrob Chemother 51: 757-759 [Full Text]
Dey, B., Del Castillo, C. S., Berger, E. A. (2003). Neutralization of Human Immunodeficiency Virus Type 1 by sCD4-17b, a Single-Chain Chimeric Protein, Based on Sequential Interaction of gp120 with CD4 and Coreceptor. J. Virol. 77: 2859-2865 [Abstract] [Full Text]
Vinner, L., Wee, E. G.-T., Patel, S., Corbet, S., Gao, G. P., Nielsen, C., Wilson, J. M., Ertl, H. C. J., Hanke, T., Fomsgaard, A. (2003). Immunogenicity in Mamu-A*01 rhesus macaques of a CCR5-tropic human immunodeficiency virus type 1 envelope from the primary isolate (Bx08) after synthetic DNA prime and recombinant adenovirus 5 boost. J. Gen. Virol. 84: 203-213 [Abstract] [Full Text]
Hart, M. L., Saifuddin, M., Spear, G. T. (2003). Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin. J. Gen. Virol. 84: 353-360 [Abstract] [Full Text]
Herrera, C., Spenlehauer, C., Fung, M. S., Burton, D. R., Beddows, S., Moore, J. P. (2002). Nonneutralizing Antibodies to the CD4-Binding Site on the gp120 Subunit of Human Immunodeficiency Virus Type 1 Do Not Interfere with the Activity of a Neutralizing Antibody against the Same Site. J. Virol. 77: 1084-1091 [Abstract] [Full Text]
Pantophlet, R., Ollmann Saphire, E., Poignard, P., Parren, P. W. H. I., Wilson, I. A., Burton, D. R. (2002). Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol. 77: 642-658 [Abstract] [Full Text]
Raja, A., Venturi, M., Kwong, P., Sodroski, J. (2002). CD4 Binding Site Antibodies Inhibit Human Immunodeficiency Virus gp120 Envelope Glycoprotein Interaction with CCR5. J. Virol. 77: 713-718 [Abstract] [Full Text]
Joyce, J. G., Hurni, W. M., Bogusky, M. J., Garsky, V. M., Liang, X., Citron, M. P., Danzeisen, R. C., Miller, M. D., Shiver, J. W., Keller, P. M. (2002). Enhancement of alpha -Helicity in the HIV-1 Inhibitory Peptide DP178 Leads to an Increased Affinity for Human Monoclonal Antibody 2F5 but Does Not Elicit Neutralizing Responses in Vitro. IMPLICATIONS FOR VACCINE DESIGN. J. Biol. Chem. 277: 45811-45820 [Abstract] [Full Text]
Hong, P. W.-P., Flummerfelt, K. B., de Parseval, A., Gurney, K., Elder, J. H., Lee, B. (2002). Human Immunodeficiency Virus Envelope (gp120) Binding to DC-SIGN and Primary Dendritic Cells Is Carbohydrate Dependent but Does Not Involve 2G12 or Cyanovirin Binding Sites: Implications for Structural Analyses of gp120-DC-SIGN Binding. J. Virol. 76: 12855-12865 [Abstract] [Full Text]
Jeffs, S. A., Shotton, C., Balfe, P., McKeating, J. A. (2002). Truncated gp120 envelope glycoprotein of human immunodeficiency virus 1 elicits a broadly reactive neutralizing immune response. J. Gen. Virol. 83: 2723-2732 [Abstract] [Full Text]

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