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 Google Scholar
Google Scholar
Right arrow Articles by Hammonds, J.
Right arrow Articles by Spearman, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hammonds, J.
Right arrow Articles by Spearman, P.

 Previous Article  |  Next Article 

Journal of Virology, December 2005, p. 14804-14814, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14804-14814.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Induction of Neutralizing Antibodies against Human Immunodeficiency Virus Type 1 Primary Isolates by Gag-Env Pseudovirion Immunization

Jason Hammonds,1 Xuemin Chen,1 Timothy Fouts,2 Anthony DeVico,2 David Montefiori,3 and Paul Spearman1*

Departments of Pediatrics and Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee,1 Division of Vaccine Research, Institute for Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland,2 Department of Surgery, Duke University, Durham, North Carolina3

Received 23 May 2005/ Accepted 15 September 2005

A major challenge for the development of an effective HIV vaccine is to elicit neutralizing antibodies against a broad array of primary isolates. Monomeric gp120-based vaccine approaches have not been successful in inducing this type of response, prompting a number of approaches designed to recreate the native glycoprotein complex that exists on the viral membrane. Gag-Env pseudovirions are noninfectious viruslike particles that recreate the native envelope glycoprotein structure and have the potential to generate neutralizing antibody responses against primary isolates. In this study, an inducible cell line was created in order to generate Gag-Env pseudovirions for examination of neutralizing antibody responses in guinea pigs. Unadjuvanted pseudovirions generated relatively weak anti-gp120 responses, while the use of a block copolymer water-in-oil emulsion or aluminum hydroxide combined with CpG oligodeoxynucleotides resulted in high levels of antibodies that bind to gp120. Sera from immunized animals neutralized a panel of human immunodeficiency virus (HIV) type 1 primary isolate viruses at titers that were significantly higher than that of the corresponding monomeric gp120 protein. Interpretation of these results was complicated by the occurrence of neutralizing antibodies directed against cellular (non-envelope protein) components of the pseudovirion. However, a major component of the pseudovirion-elicited antibody response was directed specifically against the HIV envelope. These results provide support for the role of pseudovirion-based vaccines in generating neutralizing antibodies against primary isolates of HIV and highlight the potential confounding role of antibodies directed at non-envelope cell surface components.

* Corresponding author. Mailing address: Vanderbilt University Medical Center, Pediatric Infectious Diseases, D-7235 MCN, Nashville, TN 37232-2581. Phone: (615) 343-5618. Fax: (615) 322-6782. E-mail: paul.spearman{at}vanderbilt.edu.

Journal of Virology, December 2005, p. 14804-14814, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14804-14814.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»