JVI Figure table search 04
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 Montefiori, D. C.
Right arrow Articles by Rovinski, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Montefiori, D. C.
Right arrow Articles by Rovinski, B.

 Previous Article  |  Next Article 

Journal of Virology, July 2001, p. 5879-5890, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.5879-5890.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Induction of Neutralizing Antibodies and Gag-Specific Cellular Immune Responses to an R5 Primary Isolate of Human Immunodeficiency Virus Type 1 in Rhesus Macaques

David C. Montefiori,1,* Jeffrey T. Safrit,2 Shari L. Lydy,2 Ashley P. Barry,2 Miroslawa Bilska,1 Ha T. T. Vo,1 Michel Klein,3 James Tartaglia,4 Harriet L. Robinson,2 and Benjamin Rovinski4

Department of Surgery, Duke University Medical Center, Durham, North Carolina 277101; Yerkes Regional Primate Research Center, Atlanta, Georgia 303292; Aventis Pasteur, Marcy l'Etoile, France3; and Aventis Pasteur, Willowdale, Ontario, Canada4

Received 6 December 2000/Accepted 23 March 2001

The ability to generate antibodies that cross-neutralize diverse primary isolates is an important goal for human immunodeficiency virus type 1 (HIV-1) vaccine development. Most of the candidate HIV-1 vaccines tested in humans and nonhuman primates have failed in this regard. Past efforts have focused almost entirely on the envelope glycoproteins of a small number of T-cell line-adapted strains of the virus as immunogens. Here we assessed the immunogenicity of noninfectious virus-like particles (VLP) consisting of Gag, Pro (protease), and Env from R5 primary isolate HIV-1Bx08. Immunogens were delivered to rhesus macaques in the form of either purified VLP, recombinant DNA and canarypox (ALVAC) vectors engineered to express VLP, or a combination of these products. Seroconversion to Gag and Pro was detected in all of the immunized animals. Antibodies that could neutralize HIV-1Bx08 were detected in animals that received (i) coinoculations with DNABx08 and VLPBx08, (ii) DNABx08 followed by ALVACBx08 boosting, and (iii) VLPBx08 alone. The neutralizing antibodies were highly strain specific despite the fact that they did not appear to be directed to linear epitopes in the V3 loop. Virus-specific cellular immune responses also were generated, as judged by the presence of Gag-specific gamma interferon (IFN-gamma )-producing cells. These cellular immune responses required the inclusion of DNABx08 in the immunization modality, since few or no IFN-gamma -producing cells were detected in animals that received either VLPBx08 or ALVACBx08 alone. The results demonstrate the feasibility of generating neutralizing antibodies and cellular immune responses that target an R5 primary HIV-1 isolate by vaccination in primates.

* Corresponding author. Mailing address: Department of Surgery, Box 2926, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-5278. Fax: (919) 684-4288. E-mail: monte{at}acpub.duke.edu.

Journal of Virology, July 2001, p. 5879-5890, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.5879-5890.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. Mol. Cell. Biol. Microbiol. Mol. Biol. Rev.
Clin. Vaccine Immunol. ALL ASM JOURNALS

Copyright © 2001 by the American Society for Microbiology. All rights reserved.