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 Srivastava, I. K.
Right arrow Articles by Stamatatos, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Srivastava, I. K.
Right arrow Articles by Stamatatos, L.

 Previous Article  |  Next Article 

Journal of Virology, February 2003, p. 2310-2320, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2310-2320.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Changes in the Immunogenic Properties of Soluble gp140 Human Immunodeficiency Virus Envelope Constructs upon Partial Deletion of the Second Hypervariable Region

Indresh K. Srivastava,1 Keating VanDorsten,2 Lucia Vojtech,2 Susan W. Barnett,1 and Leonidas Stamatatos2*

Chiron Corporation, Emeryville, California 94608,1 Seattle Biomedical Research Institute, University of Washington, Seattle, Washington 981032

Received 19 August 2002/ Accepted 11 November 2002

Immunization of macaques with the soluble oligomeric gp140 form of the SF162 envelope (SF162gp140) or with an SF162gp140-derived construct lacking the central region of the V2 loop ({Delta}V2gp140) results in the generation of high titers of antibodies capable of neutralizing the homologous human immunodeficiency virus type 1 (HIV-1), SF162 virus (Barnett et al. J. Virol. 75:5526-5540, 2001). However, the {Delta}V2gp140 immunogen is more effective than the SF162gp140 immunogen in eliciting the generation of antibodies capable of neutralizing heterologous HIV-1 isolates. This indicates that deletion of the V2 loop alters the immunogenicity of the SF162gp140 protein. The present studies were aimed at identifying the envelope regions whose immunogenicity is altered following V2 loop deletion. We report that the antibodies elicited by the SF162gp140 immunogen recognize elements of the V1, V2, and V3 loops, the CD4-binding site, and the C1 and C2 regions on the homologous SF162 gp120. With the exception of the V1 and V2 loops, the same regions are recognized on heterologous gp120 proteins. Surprisingly, although a minority of the SF162gp140-elicited antibodies target the V3 loop on the homologous gp120, the majority of the antibodies elicited by this immunogen that are capable of binding to the heterologous gp120s tested recognize their V3 loops. Deletion of the V2 loop has two effects. First, it alters the immunogenicity of the V3 and V1 loops, and second, it renders the C5 region immunogenic. Although deletion of the V2 loop does not result in an increase in the immunogenicity of the CD4-binding site per se, the relative ratio of anti-CD4-binding site to anti-V3 loop antibodies that bind to the heterologous gp120s tested is higher in sera collected from the {Delta}V2gp140-immunized animals than in the SF162gp140-immunized animals. Overall, our studies indicate that it is possible to alter the immunogenic structure of the HIV envelope by introducing specific modifications.

* Corresponding author. Mailing address: Seattle Biomedical Research Institute, University of Washington, 4 Nickerson St., Seattle, WA 98109. Phone: (206) 284-8846. Fax: (206) 284-0313. E-mail: lstam{at}sbri.org.

Journal of Virology, February 2003, p. 2310-2320, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2310-2320.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sundling, C., Schon, K., Morner, A., Forsell, M. N. E., Wyatt, R. T., Thorstensson, R., Hedestam, G. B. K., Lycke, N. Y. (2008). CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization. J. Gen. Virol. 89: 2954-2964 [Abstract] [Full Text]  
  • Lin, G., Bertolotti-Ciarlet, A., Haggarty, B., Romano, J., Nolan, K. M., Leslie, G. J., Jordan, A. P.-O., Huang, C.-c., Kwong, P. D., Doms, R. W., Hoxie, J. A. (2007). Replication-Competent Variants of Human Immunodeficiency Virus Type 2 Lacking the V3 Loop Exhibit Resistance to Chemokine Receptor Antagonists. J. Virol. 81: 9956-9966 [Abstract] [Full Text]  
  • Law, M., Cardoso, R. M. F., Wilson, I. A., Burton, D. R. (2007). Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy. J. Virol. 81: 4272-4285 [Abstract] [Full Text]  
  • Honnen, W. J., Krachmarov, C., Kayman, S. C., Gorny, M. K., Zolla-Pazner, S., Pinter, A. (2007). Type-Specific Epitopes Targeted by Monoclonal Antibodies with Exceptionally Potent Neutralizing Activities for Selected Strains of Human Immunodeficiency Virus Type 1 Map to a Common Region of the V2 Domain of gp120 and Differ Only at Single Positions from the Clade B Consensus Sequence. J. Virol. 81: 1424-1432 [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]  
  • Li, M., Gao, F., Mascola, J. R., Stamatatos, L., Polonis, V. R., Koutsoukos, M., Voss, G., Goepfert, P., Gilbert, P., Greene, K. M., Bilska, M., Kothe, D. L., Salazar-Gonzalez, J. F., Wei, X., Decker, J. M., Hahn, B. H., Montefiori, D. C. (2005). Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol. 79: 10108-10125 [Abstract] [Full Text]  
  • Poon, B., Hsu, J. F., Gudeman, V., Chen, I. S. Y., Grovit-Ferbas, K. (2005). Formaldehyde-Treated, Heat-Inactivated Virions with Increased Human Immunodeficiency Virus Type 1 Env Can Be Used To Induce High-Titer Neutralizing Antibody Responses. J. Virol. 79: 10210-10217 [Abstract] [Full Text]  
  • Beddows, S., Schulke, N., Kirschner, M., Barnes, K., Franti, M., Michael, E., Ketas, T., Sanders, R. W., Maddon, P. J., Olson, W. C., Moore, J. P. (2005). Evaluating the Immunogenicity of a Disulfide-Stabilized, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol. 79: 8812-8827 [Abstract] [Full Text]  
  • Otten, G. R., Schaefer, M., Doe, B., Liu, H., Srivastava, I., zur Megede, J., Kazzaz, J., Lian, Y., Singh, M., Ugozzoli, M., Montefiori, D., Lewis, M., Driver, D. A., Dubensky, T., Polo, J. M., Donnelly, J., O'Hagan, D. T., Barnett, S., Ulmer, J. B. (2005). Enhanced Potency of Plasmid DNA Microparticle Human Immunodeficiency Virus Vaccines in Rhesus Macaques by Using a Priming-Boosting Regimen with Recombinant Proteins. J. Virol. 79: 8189-8200 [Abstract] [Full Text]  
  • Brown, B. K., Darden, J. M., Tovanabutra, S., Oblander, T., Frost, J., Sanders-Buell, E., de Souza, M. S., Birx, D. L., McCutchan, F. E., Polonis, V. R. (2005). Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01_AE, and CRF02_AG, for the Development and Assessment of Candidate Vaccines. J. Virol. 79: 6089-6101 [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]  
  • Quinnan, G. V. Jr., Yu, X.-F., Lewis, M. G., Zhang, P. F., Sutter, G., Silvera, P., Dong, M., Choudhary, A., Sarkis, P. T. N., Bouma, P., Zhang, Z., Montefiori, D. C., VanCott, T. C., Broder, C. C. (2005). Protection of Rhesus Monkeys against Infection with Minimally Pathogenic Simian-Human Immunodeficiency Virus: Correlations with Neutralizing Antibodies and Cytotoxic T Cells. J. Virol. 79: 3358-3369 [Abstract] [Full Text]  
  • Varadarajan, R., Sharma, D., Chakraborty, K., Patel, M., Citron, M., Sinha, P., Yadav, R., Rashid, U., Kennedy, S., Eckert, D., Geleziunas, R., Bramhill, D., Schleif, W., Liang, X., Shiver, J. (2005). Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4D12 and gp120-M9: Implications for Targeting the CD4i Epitope in Human Immunodeficiency Virus Vaccine Design. J. Virol. 79: 1713-1723 [Abstract] [Full Text]  
  • Yang, Z.-y., Chakrabarti, B. K., Xu, L., Welcher, B., Kong, W.-p., Leung, K., Panet, A., Mascola, J. R., Nabel, G. J. (2004). Selective Modification of Variable Loops Alters Tropism and Enhances Immunogenicity of Human Immunodeficiency Virus Type 1 Envelope. J. Virol. 78: 4029-4036 [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]  
  • 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]  
  • Kong, W.-P., Huang, Y., Yang, Z.-Y., Chakrabarti, B. K., Moodie, Z., Nabel, G. J. (2003). Immunogenicity of Multiple Gene and Clade Human Immunodeficiency Virus Type 1 DNA Vaccines. J. Virol. 77: 12764-12772 [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»