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 zur Megede, J.
Right arrow Articles by Barnett, S. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by zur Megede, J.
Right arrow Articles by Barnett, S. W.

 Previous Article  |  Next Article 

Journal of Virology, June 2003, p. 6197-6207, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6197-6207.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Expression and Immunogenicity of Sequence-Modified Human Immunodeficiency Virus Type 1 Subtype B pol and gagpol DNA Vaccines

Jan zur Megede,* Gillis R. Otten, Barbara Doe, Hong Liu, Louisa Leung, Jeffrey B. Ulmer, John J. Donnelly, and Susan W. Barnett*

Chiron Corporation, Emeryville, California 94608

Received 7 October 2002/ Accepted 14 March 2003

Control of the worldwide AIDS pandemic may require not only preventive but also therapeutic immunization strategies. To meet this challenge, the next generation of human immunodeficiency virus type 1 (HIV-1) vaccines must stimulate broad and durable cellular immune responses to multiple HIV antigens. Results of both natural history studies and virus challenge studies with macaques indicate that responses to both Gag and Pol antigens are important for the control of viremia. Previously, we reported increased Rev-independent expression and improved immunogenicity of DNA vaccines encoding sequence-modified Gag derived from the HIV-1SF2 strain (J. zur Megede, M. C. Chen, B. Doe, M. Schaefer, C. E. Greer, M. Selby, G. R. Otten, and S. W. Barnett, J. Virol. 74: 2628-2635, 2000). Here we describe results of expression and immunogenicity studies conducted with novel sequence-modified HIV-1SF2 GagPol and Pol vaccine antigens. These Pol antigens contain deletions in the integrase coding region and were mutated in the reverse transcriptase (RT) coding region to remove potentially deleterious enzymatic activities. The resulting Pol sequences were used alone or in combination with sequence-modified Gag. In the latter, the natural translational frameshift between the Gag and Pol coding sequences was either retained or removed. Smaller, in-frame fusion gene cassettes expressing Gag plus RT or protease plus RT also were evaluated. Expression of Gag and Pol from GagPol fusion gene cassettes appeared to be reduced when the HIV protease was active. Therefore, additional constructs were evaluated in which mutations were introduced to attenuate or inactivate the protease activity. Nevertheless, when these constructs were delivered to mice as DNA vaccines, similar levels of CD8+ T-cell responses to Gag and Pol epitopes were observed regardless of the level of protease activity. Overall, the cellular immune responses against Gag induced in mice immunized with multigenic gagpol plasmids were similar to those observed in mice immunized with the plasmid encoding Gag alone. Furthermore, all of the sequence-modified pol and gagpol plasmids expressed high levels of Pol-specific antigens in a Rev-independent fashion and were able to induce potent Pol-specific T- and B-cell responses in mice. These results support the inclusion of a gagpol in-frame fusion gene in future HIV vaccine approaches.

* Corresponding author. Mailing address: Chiron Corporation, Mail Stop 4.3, 4560 Horton St., Emeryville, CA 94608. Phone: (510) 923-7729 (Jan zur Megede) or (510) 923-7565 (Susan Barnett). Fax: (510) 923-2586. E-mail: Jan_zur_Megede{at}chiron.com or Susan_Barnett{at}chiron.com.

Journal of Virology, June 2003, p. 6197-6207, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6197-6207.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Donnelly, J. J., Wahren, B., Liu, M. A. (2005). DNA Vaccines: Progress and Challenges. J. Immunol. 175: 633-639 [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»