Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG

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J. Virol., 11 1995, 6609-6617, Vol 69, No. 11
Copyright © 1995, American Society for Microbiology

Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG

A Trkola, AB Pomales, H Yuan, B Korber, PJ Maddon, GP Allaway, H Katinger, CF Barbas 3rd, DR Burton and DD Ho
Aaron Diamond AIDS Research Center, New York University School of Medicine, New York 10016, USA.

We have tested three human monoclonal antibodies (MAbs) IgG1b12, 2G12, and 2F5) to the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1), and a tetrameric CD4-IgG molecule (CD4-IgG2), for the ability to neutralize primary HIV-1 isolates from the genetic clades A through F and from group O. Each of the reagents broadly and potently neutralized B-clade isolates. The 2F5 MAb and the CD4-IgG2 molecule also neutralized strains from outside the B clade, with the same breadth and potency that they showed against B-clade strains. The other two MAbs were able to neutralize a significant proportion of strains from outside the B clade, although there was a reduction in their efficacy compared with their activity against B-clade isolates. Neutralization of isolates by 2F5 correlated with their possession of the LDKW motif in a segment of gp41 near the membrane-spanning domain. The other two MAbs and CD4-IgG2 recognize discontinuous binding sites on gp120, and so no comparison between genetic sequence and virus neutralization was possible. Our data show that a vaccine based on the induction of humoral immunity that is broadly active across the genetic clades is not possible if immunogens that express the epitopes for MAbs such as 2F5, 2G12, and IgG1b12 in immunogenic configurations can be created. Furthermore, if the three MAbs and CD4-IgG2 produce clinical benefit in immunotherapeutic trials in the United States or Europe, they may also do so elsewhere in the world.

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Parker, C. E., Deterding, L. J., Hager-Braun, C., Binley, J. M., Schulke, N., Katinger, H., Moore, J. P., Tomer, K. B. (2001). Fine Definition of the Epitope on the gp41 Glycoprotein of Human Immunodeficiency Virus Type 1 for the Neutralizing Monoclonal Antibody 2F5. J. Virol. 75: 10906-10911 [Abstract] [Full Text]
Finnegan, C. M., Berg, W., Lewis, G. K., DeVico, A. L. (2001). Antigenic Properties of the Human Immunodeficiency Virus Envelope during Cell-Cell Fusion. J. Virol. 75: 11096-11105 [Abstract] [Full Text]
Verrier, F., Nadas, A., Gorny, M. K., Zolla-Pazner, S. (2001). Additive Effects Characterize the Interaction of Antibodies Involved in Neutralization of the Primary Dualtropic Human Immunodeficiency Virus Type 1 Isolate 89.6. J. Virol. 75: 9177-9186 [Abstract] [Full Text]
Clapham, P. R, McKnight, A. (2001). HIV-1 receptors and cell tropism. Br Med Bull 58: 43-59 [Abstract] [Full Text]
Parren, P. W. H. I., Marx, P. A., Hessell, A. J., Luckay, A., Harouse, J., Cheng-Mayer, C., Moore, J. P., Burton, D. R. (2001). Antibody Protects Macaques against Vaginal Challenge with a Pathogenic R5 Simian/Human Immunodeficiency Virus at Serum Levels Giving Complete Neutralization In Vitro. J. Virol. 75: 8340-8347 [Abstract] [Full Text]
Hofmann-Lehmann, R., Vlasak, J., Rasmussen, R. A., Smith, B. A., Baba, T. W., Liska, V., Ferrantelli, F., Montefiori, D. C., McClure, H. M., Anderson, D. C., Bernacky, B. J., Rizvi, T. A., Schmidt, R., Hill, L. R., Keeling, M. E., Katinger, H., Stiegler, G., Cavacini, L. A., Posner, M. R., Chou, T.-C., Andersen, J., Ruprecht, R. M. (2001). Postnatal Passive Immunization of Neonatal Macaques with a Triple Combination of Human Monoclonal Antibodies against Oral Simian-Human Immunodeficiency Virus Challenge. J. Virol. 75: 7470-7480 [Abstract] [Full Text]
Saphire, E. O., Parren, P. W. H. I., Pantophlet, R., Zwick, M. B., Morris, G. M., Rudd, P. M., Dwek, R. A., Stanfield, R. L., Burton, D. R., Wilson, I. A. (2001). Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design. Science 293: 1155-1159 [Abstract] [Full Text]
Zhu, P., Olson, W. C., Roux, K. H. (2001). Structural Flexibility and Functional Valence of CD4-IgG2 (PRO 542): Potential for Cross-Linking Human Immunodeficiency Virus Type 1 Envelope Spikes. J. Virol. 75: 6682-6686 [Abstract] [Full Text]
Zwick, M. B., Bonnycastle, L. L. C., Menendez, A., Irving, M. B., Barbas, C. F. III, Parren, P. W. H. I., Burton, D. R., Scott, J. K. (2001). Identification and Characterization of a Peptide That Specifically Binds the Human, Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody b12. J. Virol. 75: 6692-6699 [Abstract] [Full Text]
Moore, J. P., Parren, P. W. H. I., Burton, D. R. (2001). Genetic Subtypes, Humoral Immunity, and Human Immunodeficiency Virus Type 1 Vaccine Development. J. Virol. 75: 5721-5729 [Full Text]
Burrer, R., Salmon-Ceron, D., Richert, S., Pancino, G., Spiridon, G., Haessig, S., Roques, V., Barre-Sinoussi, F., Aubertin, A.-M., Moog, C. (2001). Immunoglobulin G (IgG) and IgA, but also Nonantibody Factors, Account for In Vitro Neutralization of Human Immunodeficiency Virus (HIV) Type 1 Primary Isolates by Serum and Plasma of HIV-Infected Patients. J. Virol. 75: 5421-5424 [Abstract] [Full Text]
Cho, M. W., Kim, Y. B., Lee, M. K., Gupta, K. C., Ross, W., Plishka, R., Buckler-White, A., Igarashi, T., Theodore, T., Byrum, R., Kemp, C., Montefiori, D. C., Martin, M. A. (2001). Polyvalent Envelope Glycoprotein Vaccine Elicits a Broader Neutralizing Antibody Response but Is Unable To Provide Sterilizing Protection against Heterologous Simian/Human Immunodeficiency Virus Infection in Pigtailed Macaques. J. Virol. 75: 2224-2234 [Abstract] [Full Text]
Spenlehauer, C., Kirn, A., Aubertin, A.-M., Moog, C. (2001). Antibody-Mediated Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates: Investigation of the Mechanism of Inhibition. J. Virol. 75: 2235-2245 [Abstract] [Full Text]
Trkola, A., Ketas, T. J., Nagashima, K. A., Zhao, L., Cilliers, T., Morris, L., Moore, J. P., Maddon, P. J., Olson, W. C. (2001). Potent, Broad-Spectrum Inhibition of Human Immunodeficiency Virus Type 1 by the CCR5 Monoclonal Antibody PRO 140. J. Virol. 75: 579-588 [Abstract] [Full Text]
Nyambi, P. N., Mbah, H. A., Burda, S., Williams, C., Gorny, M. K., Nádas, A., Zolla-Pazner, S. (2000). Conserved and Exposed Epitopes on Intact, Native, Primary Human Immunodeficiency Virus Type 1 Virions of Group M. J. Virol. 74: 7096-7107 [Abstract] [Full Text]
D'Souza, M. P., Cairns, J. S., Plaeger, S. F. (2000). Current Evidence and Future Directions for Targeting HIV Entry: Therapeutic and Prophylactic Strategies. JAMA 284: 215-222 [Abstract] [Full Text]
Gorny, M. K., Zolla-Pazner, S. (2000). Recognition by Human Monoclonal Antibodies of Free and Complexed Peptides Representing the Prefusogenic and Fusogenic Forms of Human Immunodeficiency Virus Type 1 gp41. J. Virol. 74: 6186-6192 [Abstract] [Full Text]
Sanders, R. W., Schiffner, L., Master, A., Kajumo, F., Guo, Y., Dragic, T., Moore, J. P., Binley, J. M. (2000). Variable-Loop-Deleted Variants of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Can Be Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits. J. Virol. 74: 5091-5100 [Abstract] [Full Text]
Moulard, M., Lortat-Jacob, H., Mondor, I., Roca, G., Wyatt, R., Sodroski, J., Zhao, L., Olson, W., Kwong, P. D., Sattentau, Q. J. (2000). Selective Interactions of Polyanions with Basic Surfaces on Human Immunodeficiency Virus Type 1 gp120. J. Virol. 74: 1948-1960 [Abstract] [Full Text]
Binley, J. M., Sanders, R. W., Clas, B., Schuelke, N., Master, A., Guo, Y., Kajumo, F., Anselma, D. J., Maddon, P. J., Olson, W. C., Moore, J. P. (2000). A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure. J. Virol. 74: 627-643 [Abstract] [Full Text]
Crawford, J. M., Earl, P. L., Moss, B., Reimann, K. A., Wyand, M. S., Manson, K. H., Bilska, M., Zhou, J. T., Pauza, C. D., Parren, P. W. H. I., Burton, D. R., Sodroski, J. G., Letvin, N. L., Montefiori, D. C. (1999). Characterization of Primary Isolate-Like Variants of Simian-Human Immunodeficiency Virus. J. Virol. 73: 10199-10207 [Abstract] [Full Text]
Trkola, A., Matthews, J., Gordon, C., Ketas, T., Moore, J. P. (1999). A Cell Line-Based Neutralization Assay for Primary Human Immunodeficiency Virus Type 1 Isolates That Use either the CCR5 or the CXCR4 Coreceptor. J. Virol. 73: 8966-8974 [Abstract] [Full Text]
Polacino, P. S., Stallard, V., Klaniecki, J. E., Pennathur, S., Montefiori, D. C., Langlois, A. J., Richardson, B. A., Morton, W. R., Benveniste, R. E., Hu, S.-L. (1999). Role of Immune Responses against the Envelope and the Core Antigens of Simian Immunodeficiency Virus SIVmne in Protection against Homologous Cloned and Uncloned Virus Challenge in Macaques. J. Virol. 73: 8201-8215 [Abstract] [Full Text]
Mascola, J. R., Lewis, M. G., Stiegler, G., Harris, D., VanCott, T. C., Hayes, D., Louder, M. K., Brown, C. R., Sapan, C. V., Frankel, S. S., Lu, Y., Robb, M. L., Katinger, H., Birx, D. L. (1999). Protection of Macaques against Pathogenic Simian/Human Immunodeficiency Virus 89.6PD by Passive Transfer of Neutralizing Antibodies. J. Virol. 73: 4009-4018 [Abstract] [Full Text]
Zolla-Pazner, S., Gorny, M. K., Nyambi, P. N., VanCott, T. C., Nádas, A. (1999). Immunotyping of Human Immunodeficiency Virus Type 1�(HIV): an Approach to Immunologic Classification of HIV. J. Virol. 73: 4042-4051 [Abstract] [Full Text]
Beddows, S., Lister, S., Cheingsong, R., Bruck, C., Weber, J. (1999). Comparison of the Antibody Repertoire Generated in Healthy Volunteers following Immunization with a Monomeric Recombinant gp120 Construct Derived from a CCR5/CXCR4-Using Human Immunodeficiency Virus Type 1�Isolate with Sera from Naturally Infected Individuals. J. Virol. 73: 1740-1745 [Abstract] [Full Text]
Gordon, C. J., Muesing, M. A., Proudfoot, A. E.�I., Power, C. A., Moore, J. P., Trkola, A. (1999). Enhancement of Human Immunodeficiency Virus Type 1�Infection by the CC-Chemokine RANTES Is Independent of the Mechanism of Virus-Cell Fusion. J. Virol. 73: 684-694 [Abstract] [Full Text]
Frankel, S. S., Steinman, R. M., Michael, N. L., Kim, S. R., Bhardwaj, N., Pope, M., Louder, M. K., Ehrenberg, P. K., Parren, P. W.�H.�I., Burton, D. R., Katinger, H., VanCott, T. C., Robb, M. L., Birx, D. L., Mascola, J. R. (1998). Neutralizing Monoclonal Antibodies Block Human Immunodeficiency Virus Type 1�Infection of Dendritic Cells and Transmission to T Cells. J. Virol. 72: 9788-9794 [Abstract] [Full Text]
Spenlehauer, C., Saragosti, S., Fleury, H. J.�A., Kirn, A., Aubertin, A.-M., Moog, C. (1998). Study of the V3 Loop as a Target Epitope for Antibodies Involved in the Neutralization of Primary Isolates versus T-Cell-Line-Adapted Strains of Human Immunodeficiency Virus Type 1. J. Virol. 72: 9855-9864 [Abstract] [Full Text]
Parren, P. W.�H.�I., Wang, M., Trkola, A., Binley, J. M., Purtscher, M., Katinger, H., Moore, J. P., Burton, D. R. (1998). Antibody Neutralization-Resistant Primary Isolates of Human Immunodeficiency Virus Type 1. J. Virol. 72: 10270-10274 [Abstract] [Full Text]
Rossio, J. L., Esser, M. T., Suryanarayana, K., Schneider, D. K., Bess, J. W. Jr., Vasquez, G. M., Wiltrout, T. A., Chertova, E., Grimes, M. K., Sattentau, Q., Arthur, L. O., Henderson, L. E., Lifson, J. D. (1998). Inactivation of Human Immunodeficiency Virus Type 1�Infectivity with Preservation of Conformational and Functional Integrity of Virion Surface Proteins. J. Virol. 72: 7992-8001 [Abstract] [Full Text]

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