This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zwick, M. B.
Right arrow Articles by Parren, P. W. H. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zwick, M. B.
Right arrow Articles by Parren, P. W. H. I.

 Previous Article  |  Next Article 

Journal of Virology, December 2001, p. 12198-12208, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12198-12208.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Neutralization Synergy of Human Immunodeficiency Virus Type 1 Primary Isolates by Cocktails of Broadly Neutralizing Antibodies

Michael B. Zwick,1 Meng Wang,1 Pascal Poignard,1 Gabriela Stiegler,2 Hermann Katinger,2 Dennis R. Burton,1 and Paul W. H. I. Parren1,*

Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037,1 and Institute for Applied Microbiology, University of Agriculture, Vienna, Austria2

Received 6 July 2001/Accepted 17 September 2001

Several reports have described the existence of synergy between neutralizing monoclonal antibodies (MAbs) against human immunodeficiency virus type 1 (HIV-1). Synergy between human MAbs b12, 2G12, 2F5, and 4E10 in neutralization of primary isolates is of particular interest. Neutralization synergy of these MAbs, however, has not been studied extensively, and the mechanism of synergy remains unclear. We investigated neutralization synergy among this human antibody set by using the classical approach of titrating antibodies mixed at a fixed ratio as well as by an alternative, variable ratio approach in which the neutralization curve of one MAb is assessed in the presence and absence of a fixed, weakly neutralizing concentration of a second antibody. The advantage of this second approach is that it does not require mathematical analysis to establish synergy. No neutralization enhancement of any of the MAb combinations tested was detected for the T-cell-line-adapted molecular HIV-1 clone HxB2 using both assay formats. Studies of primary isolates (89.6, SF162, and JR-CSF) showed neutralization synergy which was relatively weak, with a maximum of two- to fourfold enhancement between antibody pairs, thereby increasing neutralization titers about 10-fold in triple and quadruple antibody combinations. Analysis of b12 and 2G12 binding to oligomeric envelope glycoprotein by using flow cytometry failed to demonstrate cooperativity in binding between these two antibodies. The mechanism by which these antibodies synergize is, therefore, not yet understood. The results lend some support to the notion that an HIV-1 vaccine that elicits moderate neutralizing antibodies to multiple epitopes may be more effective than hereto supposed, although considerable caution in extrapolating to a vaccine situation is required.

* Corresponding author. Mailing address: The Scripps Research Institute, Department of Immunology, 10550 N. Torrey Pines Rd., IMM2, La Jolla, CA 92037. Phone: (858) 784-8602. Fax: (858) 784-8360. E-mail: parren{at}scripps.edu.

Journal of Virology, December 2001, p. 12198-12208, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12198-12208.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Pantophlet, R., Wang, M., Aguilar-Sino, R. O., Burton, D. R. (2009). The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions. J. Virol. 83: 1649-1659 [Abstract] [Full Text]  
  • Luo, X. M., Maarschalk, E., O'Connell, R. M., Wang, P., Yang, L., Baltimore, D. (2009). Engineering human hematopoietic stem/progenitor cells to produce a broadly neutralizing anti-HIV antibody after in vitro maturation to human B lymphocytes.. Blood 113: 1422-1431 [Abstract] [Full Text]  
  • Montero, M., van Houten, N. E., Wang, X., Scott, J. K. (2008). The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design. Microbiol. Mol. Biol. Rev. 72: 54-84 [Abstract] [Full Text]  
  • Manrique, A., Rusert, P., Joos, B., Fischer, M., Kuster, H., Leemann, C., Niederost, B., Weber, R., Stiegler, G., Katinger, H., Gunthard, H. F., Trkola, A. (2007). In Vivo and In Vitro Escape from Neutralizing Antibodies 2G12, 2F5, and 4E10. J. Virol. 81: 8793-8808 [Abstract] [Full Text]  
  • Alam, S. M., McAdams, M., Boren, D., Rak, M., Scearce, R. M., Gao, F., Camacho, Z. T., Gewirth, D., Kelsoe, G., Chen, P., Haynes, B. F. (2007). The Role of Antibody Polyspecificity and Lipid Reactivity in Binding of Broadly Neutralizing Anti-HIV-1 Envelope Human Monoclonal Antibodies 2F5 and 4E10 to Glycoprotein 41 Membrane Proximal Envelope Epitopes. J. Immunol. 178: 4424-4435 [Abstract] [Full Text]  
  • Hager-Braun, C., Katinger, H., Tomer, K. B. (2006). The HIV-Neutralizing Monoclonal Antibody 4E10 Recognizes N-Terminal Sequences on the Native Antigen.. J. Immunol. 176: 7471-7481 [Abstract] [Full Text]  
  • Lip, K.-M., Shen, S., Yang, X., Keng, C.-T., Zhang, A., Oh, H.-L. J., Li, Z.-H., Hwang, L.-A., Chou, C.-F., Fielding, B. C., Tan, T. H. P., Mayrhofer, J., Falkner, F. G., Fu, J., Lim, S. G., Hong, W., Tan, Y.-J. (2006). Monoclonal Antibodies Targeting the HR2 Domain and the Region Immediately Upstream of the HR2 of the S Protein Neutralize In Vitro Infection of Severe Acute Respiratory Syndrome Coronavirus. J. Virol. 80: 941-950 [Abstract] [Full Text]  
  • Huerta, L., Gomez-Icazbalceta, G., Soto-Ramirez, L., Viveros-Rogel, M., Rodriguez, R., Fuentes, L., Lamoyi, E., Larralde, C. (2005). Human immunodeficiency virus 1 (HIV-1) envelope-dependent cell-cell fusion modulation by HIV-positive sera is related to disease progression. J. Gen. Virol. 86: 1961-1966 [Abstract] [Full Text]  
  • Poon, B., Safrit, J. T., McClure, H., Kitchen, C., Hsu, J. F., Gudeman, V., Petropoulos, C., Wrin, T., Chen, I. S. Y., Grovit-Ferbas, K. (2005). Induction of Humoral Immune Responses following Vaccination with Envelope-Containing, Formaldehyde-Treated, Thermally Inactivated Human Immunodeficiency Virus Type 1. J. Virol. 79: 4927-4935 [Abstract] [Full Text]  
  • Yang, X., Kurteva, S., Lee, S., Sodroski, J. (2005). Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1. J. Virol. 79: 3500-3508 [Abstract] [Full Text]  
  • Zwick, M. B., Jensen, R., Church, S., Wang, M., Stiegler, G., Kunert, R., Katinger, H., Burton, D. R. (2005). Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Antibodies 2F5 and 4E10 Require Surprisingly Few Crucial Residues in the Membrane-Proximal External Region of Glycoprotein gp41 To Neutralize HIV-1. J. Virol. 79: 1252-1261 [Abstract] [Full Text]  
  • Binley, J. M., Wrin, T., Korber, B., Zwick, M. B., Wang, M., Chappey, C., Stiegler, G., Kunert, R., Zolla-Pazner, S., Katinger, H., Petropoulos, C. J., Burton, D. R. (2004). Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. J. Virol. 78: 13232-13252 [Abstract] [Full Text]  
  • Lopez-Bueno, A., Valle, N., Gallego, J. M., Perez, J., Almendral, J. M. (2004). Enhanced Cytoplasmic Sequestration of the Nuclear Export Receptor CRM1 by NS2 Mutations Developed in the Host Regulates Parvovirus Fitness. J. Virol. 78: 10674-10684 [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]  
  • Zwick, M. B., Komori, H. K., Stanfield, R. L., Church, S., Wang, M., Parren, P. W. H. I., Kunert, R., Katinger, H., Wilson, I. A., Burton, D. R. (2004). The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5. J. Virol. 78: 3155-3161 [Abstract] [Full Text]  
  • Center, R. J., Lebowitz, J., Leapman, R. D., Moss, B. (2004). Promoting Trimerization of Soluble Human Immunodeficiency Virus Type 1 (HIV-1) Env through the Use of HIV-1/Simian Immunodeficiency Virus Chimeras. J. Virol. 78: 2265-2276 [Abstract] [Full Text]  
  • Moore, J. P., Shattock, R. J. (2003). Preventing HIV-1 sexual transmission--not sexy enough science, or no benefit to the bottom line?. J Antimicrob Chemother 52: 890-892 [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]  
  • Bouma, P., Leavitt, M., Zhang, P. F., Sidorov, I. A., Dimitrov, D. S., Quinnan, G. V. Jr. (2003). Multiple Interactions across the Surface of the gp120 Core Structure Determine the Global Neutralization Resistance Phenotype of Human Immunodeficiency Virus Type 1. J. Virol. 77: 8061-8071 [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]  
  • 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]  
  • Lopez-Bueno, A., Mateu, M. G., Almendral, J. M. (2003). High Mutant Frequency in Populations of a DNA Virus Allows Evasion from Antibody Therapy in an Immunodeficient Host. J. Virol. 77: 2701-2708 [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]  
  • Poignard, P., Moulard, M., Golez, E., Vivona, V., Franti, M., Venturini, S., Wang, M., Parren, P. W. H. I., Burton, D. R. (2002). Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies. J. Virol. 77: 353-365 [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]  
  • Nowakowski, A., Wang, C., Powers, D. B., Amersdorfer, P., Smith, T. J., Montgomery, V. A., Sheridan, R., Blake, R., Smith, L. A., Marks, J. D. (2002). Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody. Proc. Natl. Acad. Sci. USA 99: 11346-11350 [Abstract] [Full Text]  
  • Lewis, A. D., Chen, R., Montefiori, D. C., Johnson, P. R., Clark, K. R. (2002). Generation of Neutralizing Activity against Human Immunodeficiency Virus Type 1 in Serum by Antibody Gene Transfer. J. Virol. 76: 8769-8775 [Abstract] [Full Text]  
  • Gaschen, B., Taylor, J., Yusim, K., Foley, B., Gao, F., Lang, D., Novitsky, V., Haynes, B., Hahn, B. H., Bhattacharya, T., Korber, B. (2002). Diversity Considerations in HIV-1 Vaccine Selection. Science 296: 2354-2360 [Abstract] [Full Text]  
  • Scanlan, C. N., Pantophlet, R., Wormald, M. R., Ollmann Saphire, E., Stanfield, R., Wilson, I. A., Katinger, H., Dwek, R. A., Rudd, P. M., Burton, D. R. (2002). The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2G12 Recognizes a Cluster of {alpha}1->2 Mannose Residues on the Outer Face of gp120. J. Virol. 76: 7306-7321 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»