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 Gao, F.
Right arrow Articles by Haynes, B. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gao, F.
Right arrow Articles by Haynes, B. F.

 Previous Article  |  Next Article 

Journal of Virology, January 2005, p. 1154-1163, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1154-1163.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein

Feng Gao,1* Eric A. Weaver,1 Zhongjing Lu,1 Yingying Li,2 Hua-Xin Liao,1 Benjiang Ma,1 S. Munir Alam,1 Richard M. Scearce,1 Laura L. Sutherland,1 Jae-Sung Yu,1 Julie M. Decker,3 George M. Shaw,3 David C. Montefiori,4 Bette T. Korber,5 Beatrice H. Hahn,2 and Barton F. Haynes1*

Departments of Medicine,1 Surgery, Duke University Medical Center, Durham, North Carolina,4 Department of Medicine, University of Alabama at Birmingham,2 Howard Hughes Medical Institute, Birmingham, Alabama,3 Los Alamos National Laboratory, Los Alamos, New Mexico5

Received 24 May 2004/ Accepted 3 September 2004

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 subtypes. When used as a DNA vaccine followed by a recombinant vaccinia virus boost in BALB/c mice, CON6 env gp120 and gp140CF elicited gamma interferon-producing T-cell responses that recognized epitopes within overlapping peptide pools from three HIV-1 Env proteins, CON6, MN (subtype B), and Chn19 (subtype C). Sera from guinea pigs immunized with recombinant CON6 Env gp120 and gp140CF glycoproteins weakly neutralized selected HIV-1 primary isolates. Thus, the computer-generated "consensus" env genes are capable of expressing envelope glycoproteins that retain the structural, functional, and immunogenic properties of wild-type HIV-1 envelopes.

* Corresponding author. Mailing address for Feng Gao: Duke University Medical Center, 112 Research Park III, Research Dr., Box 3347, Durham, NC 27710. Phone: (919) 668-6433. Fax: (919) 668-6435. E-mail: fgao{at}duke.edu. Mailing address for Barton F. Haynes: Duke University Medical Center, 215 CARL Building, Research Dr., Box 3258, Durham, NC 27710. Phone: (919) 684-5384. Fax: (919) 681-8992. E-mail: hayne002{at}mc.duke.edu.

Journal of Virology, January 2005, p. 1154-1163, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1154-1163.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Korber, B. T., Letvin, N. L., Haynes, B. F. (2009). T-Cell Vaccine Strategies for Human Immunodeficiency Virus, the Virus with a Thousand Faces. J. Virol. 83: 8300-8314 [Full Text]  
  • Kong, W.-P., Wu, L., Wallstrom, T. C., Fischer, W., Yang, Z.-Y., Ko, S.-Y., Letvin, N. L., Haynes, B. F., Hahn, B. H., Korber, B., Nabel, G. J. (2009). Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination. J. Virol. 83: 2201-2215 [Abstract] [Full Text]  
  • Binley, J. M., Lybarger, E. A., Crooks, E. T., Seaman, M. S., Gray, E., Davis, K. L., Decker, J. M., Wycuff, D., Harris, L., Hawkins, N., Wood, B., Nathe, C., Richman, D., Tomaras, G. D., Bibollet-Ruche, F., Robinson, J. E., Morris, L., Shaw, G. M., Montefiori, D. C., Mascola, J. R. (2008). Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C. J. Virol. 82: 11651-11668 [Abstract] [Full Text]  
  • Laird, M. E., Igarashi, T., Martin, M. A., Desrosiers, R. C. (2008). Importance of the V1/V2 Loop Region of Simian-Human Immunodeficiency Virus Envelope Glycoprotein gp120 in Determining the Strain Specificity of the Neutralizing Antibody Response. J. Virol. 82: 11054-11065 [Abstract] [Full Text]  
  • Santra, S., Korber, B. T., Muldoon, M., Barouch, D. H., Nabel, G. J., Gao, F., Hahn, B. H., Haynes, B. F., Letvin, N. L. (2008). A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys. Proc. Natl. Acad. Sci. USA 105: 10489-10494 [Abstract] [Full Text]  
  • Kraft, Z., Strouss, K., Sutton, W. F., Cleveland, B., Tso, F. Y., Polacino, P., Overbaugh, J., Hu, S.-L., Stamatatos, L. (2008). Characterization of Neutralizing Antibody Responses Elicited by Clade A Envelope Immunogens Derived from Early Transmitted Viruses. J. Virol. 82: 5912-5921 [Abstract] [Full Text]  
  • Azizi, A., Anderson, D. E., Torres, J. V., Ogrel, A., Ghorbani, M., Soare, C., Sandstrom, P., Fournier, J., Diaz-Mitoma, F. (2008). Induction of Broad Cross-Subtype-Specific HIV-1 Immune Responses by a Novel Multivalent HIV-1 Peptide Vaccine in Cynomolgus Macaques. J. Immunol. 180: 2174-2186 [Abstract] [Full Text]  
  • Ching, L. K., Vlachogiannis, G., Bosch, K. A., Stamatatos, L. (2008). The First Hypervariable Region of the gp120 Env Glycoprotein Defines the Neutralizing Susceptibility of Heterologous Human Immunodeficiency Virus Type 1 Isolates to Neutralizing Antibodies Elicited by the SF162gp140 Immunogen. J. Virol. 82: 949-956 [Abstract] [Full Text]  
  • Frahm, N., Kaufmann, D. E., Yusim, K., Muldoon, M., Kesmir, C., Linde, C. H., Fischer, W., Allen, T. M., Li, B., McMahon, B. H., Faircloth, K. L., Hewitt, H. S., Mackey, E. W., Miura, T., Khatri, A., Wolinsky, S., McMichael, A., Funkhouser, R. K., Walker, B. D., Brander, C., Korber, B. T. (2007). Increased Sequence Diversity Coverage Improves Detection of HIV-Specific T Cell Responses. J. Immunol. 179: 6638-6650 [Abstract] [Full Text]  
  • Buonaguro, L., Tornesello, M. L., Buonaguro, F. M. (2007). Human Immunodeficiency Virus Type 1 Subtype Distribution in the Worldwide Epidemic: Pathogenetic and Therapeutic Implications. J. Virol. 81: 10209-10219 [Full Text]  
  • Yu, J.-S., Peacock, J. W., Jacobs, W. R. Jr., Frothingham, R., Letvin, N. L., Liao, H.-X., Haynes, B. F. (2007). Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Elicits Human Immunodeficiency Virus Type 1 Envelope-Specific T Lymphocytes at Mucosal Sites. CVI 14: 886-893 [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]  
  • Dai, M., Fisher, H. E., Temirov, J., Kiss, C., Phipps, M. E., Pavlik, P., Werner, J. H., Bradbury, A. R.M. (2007). The creation of a novel fluorescent protein by guided consensus engineering. Protein Eng Des Sel 0: gzl056v1-11 [Abstract] [Full Text]  
  • Yu, J.-S., Peacock, J. W., Vanleeuwen, S., Hsu, T., Jacobs, W. R. Jr., Cayabyab, M. J., Letvin, N. L., Frothingham, R., Staats, H. F., Liao, H.-X., Haynes, B. F. (2006). Generation of Mucosal Anti-Human Immunodeficiency Virus Type 1 T-Cell Responses by Recombinant Mycobacterium smegmatis{triangledown}. CVI 13: 1204-1211 [Abstract] [Full Text]  
  • Derby, N. R., Kraft, Z., Kan, E., Crooks, E. T., Barnett, S. W., Srivastava, I. K., Binley, J. M., Stamatatos, L. (2006). Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection.. J. Virol. 80: 8745-8762 [Abstract] [Full Text]  
  • Weaver, E. A., Lu, Z., Camacho, Z. T., Moukdar, F., Liao, H.-X., Ma, B.-J., Muldoon, M., Theiler, J., Nabel, G. J., Letvin, N. L., Korber, B. T., Hahn, B. H., Haynes, B. F., Gao, F. (2006). Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen. J. Virol. 80: 6745-6756 [Abstract] [Full Text]  
  • Burgers, W. A., van Harmelen, J. H., Shephard, E., Adams, C., Mgwebi, T., Bourn, W., Hanke, T., Williamson, A.-L., Williamson, C. (2006). Design and preclinical evaluation of a multigene human immunodeficiency virus type 1 subtype C DNA vaccine for clinical trial. J. Gen. Virol. 87: 399-410 [Abstract] [Full Text]  
  • Li, Y., Svehla, K., Mathy, N. L., Voss, G., Mascola, J. R., Wyatt, R. (2006). Characterization of Antibody Responses Elicited by Human Immunodeficiency Virus Type 1 Primary Isolate Trimeric and Monomeric Envelope Glycoproteins in Selected Adjuvants. J. Virol. 80: 1414-1426 [Abstract] [Full Text]  
  • Hegde, R., Liu, Z., Mackay, G., Smith, M., Chebloune, Y., Narayan, O., Singh, D. K. (2005). Antigen Expression Kinetics and Immune Responses of Mice Immunized with Noninfectious Simian-Human Immunodeficiency Virus DNA. J. Virol. 79: 14688-14697 [Abstract] [Full Text]  
  • Huang, C.-c., Tang, M., Zhang, M.-Y., Majeed, S., Montabana, E., Stanfield, R. L., Dimitrov, D. S., Korber, B., Sodroski, J., Wilson, I. A., Wyatt, R., Kwong, P. D. (2005). Structure of a V3-Containing HIV-1 gp120 Core. Science 310: 1025-1028 [Abstract] [Full Text]  
  • Doria-Rose, N. A., Learn, G. H., Rodrigo, A. G., Nickle, D. C., Li, F., Mahalanabis, M., Hensel, M. T., McLaughlin, S., Edmonson, P. F., Montefiori, D., Barnett, S. W., Haigwood, N. L., Mullins, J. I. (2005). Human Immunodeficiency Virus Type 1 Subtype B Ancestral Envelope Protein Is Functional and Elicits Neutralizing Antibodies in Rabbits Similar to Those Elicited by a Circulating Subtype B Envelope. J. Virol. 79: 11214-11224 [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»