This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lian, Y. Articles by Barnett, S. W. Search for Related Content PubMed PubMed Citation Articles by Lian, Y. Articles by Barnett, S. W.

 Previous Article  |  Next Article 

Journal of Virology, November 2005, p. 13338-13349, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13338-13349.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Evaluation of Envelope Vaccines Derived from the South African Subtype C Human Immunodeficiency Virus Type 1 TV1 Strain

Ying Lian,¹ Indresh Srivastava,¹ V. Rául Gómez-Román,¹ Jan zur Megede,¹ Yide Sun,¹ Elaine Kan,¹ Susan Hilt,¹ Susan Engelbrecht,² Sunee Himathongkham,^3, Paul A. Luciw,³ Gillis Otten,¹ Jeffrey B. Ulmer,¹ John J. Donnelly,¹ Dietmar Rabussay,⁵ David Montefiori,⁴ Estrelita Janse van Rensburg,^2, and Susan W. Barnett^1*

Chiron Corporation, Emeryville, California 94608,¹ University of Stellenbosch, Tygerberg Hospital, Cape Town, South Africa,² University of California, Davis, California 95616,³ Duke University Medical Center, Durham, North Carolina 27710,⁴ Genetronics/Inovio, Inc., San Diego, California 92121⁵

Received 27 April 2005/ Accepted 27 July 2005

Human immunodeficiency virus type 1 (HIV-1) subtype C infections are on the rise in Sub-Saharan Africa and Asia. Therefore, there is a need to develop an HIV vaccine capable of eliciting broadly reactive immune responses against members of this subtype. We show here that modified HIV envelope (env) DNA vaccines derived from the South African subtype C TV1 strain are able to prime for humoral responses in rabbits and rhesus macaques. Priming rabbits with DNA plasmids encoding V2-deleted TV1 gp140 (gp140TV1V2), followed by boosting with oligomeric protein (o-gp140TV1V2) in MF59 adjuvant, elicited higher titers of env-binding and autologous neutralizing antibodies than priming with DNA vaccines encoding the full-length TV1 env (gp160) or the intact TV1 gp140. Immunization with V2-deleted subtype B SF162 env and V2-deleted TV1 env together using a multivalent vaccine approach induced high titers of oligomeric env-binding antibodies and autologous neutralizing antibodies against both the subtypes B and C vaccine strains, HIV-1 SF162 and TV1, respectively. Low-level neutralizing activity against the heterologous South African subtype C TV2 strain, as well as a small subset of viruses in a panel of 13 heterologous primary isolates, was observed in some rabbits immunized with the V2-deleted vaccines. Immunization of rhesus macaques with the V2-deleted TV1 DNA prime/protein boost also elicited high titers of env-binding antibodies and moderate titers of autologous TV1 neutralizing antibodies. The pilot-scale production of the various TV1 DNA vaccine constructs and env proteins described here should provide an initial platform upon which to improve the immunogenicity of these subtype C HIV envelope vaccines.

Present address: Food and Drug Laboratory, Richmond, CA 94804.

Present address: Department of Medical Virology, Tswane Academic Division, National Health Laboratory Service and University of Pretoria, Pretoria, South Africa.

This article has been cited by other articles:

• 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]  
• Holl, V., Peressin, M., Decoville, T., Schmidt, S., Zolla-Pazner, S., Aubertin, A.-M., Moog, C. (2006). Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells.. J. Virol. 80: 6177-6181 [Abstract] [Full Text]