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Journal of Virology, May 2005, p. 5537-5547, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5537-5547.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Pseudovirion Particle Production by Live Poxvirus Human Immunodeficiency Virus Vaccine Vector Enhances Humoral and Cellular Immune Responses

Xuemin Chen,¹ Michael T. Rock,¹ Jason Hammonds,¹ James Tartaglia,³ Ayumi Shintani,² Jeff Currier,⁴ Bonnie Slike,⁴ James E. Crowe Jr.,¹ Mary Marovich,⁴ and Paul Spearman^1*

Departments of Pediatrics and Microbiology and Immunology,¹ Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee,² Aventis Pasteur, Toronto, Ontario, Canada,³ U.S. Military HIV Research Program, Rockville, Maryland⁴

Received 6 September 2004/ Accepted 18 December 2004

Live-vector-based human immunodeficiency virus (HIV) vaccines are an integral part of a number of HIV vaccine regimens currently under evaluation. Live vectors that carry an intact gag gene are capable of eliciting HIV pseudovirion particle formation from infected host cells. The impact of pseudovirion particle formation on the immune response generated by live HIV vaccine vectors has not been established. In this study, a canarypox HIV vaccine candidate vector expressing HIV gag and env genes, vCP205, was modified by the introduction of a glycine-to-alanine coding change in the N-terminal myristylation site of gag to create Myr^– vCP205. This substitution effectively eliminated particle formation without altering the level of protein production. vCP205 and Myr^– vCP205 were then directly compared for the ability to induce HIV-specific immune responses in mice. The particle-competent vector vCP205 elicited higher levels of CD8⁺ T-cell responses, as indicated by gamma interferon enzyme-linked immunospot (ELISPOT) assay and intracellular cytokine staining. Humoral responses to Gag and Env were also markedly higher from animals immunized with the particle-competent vector. Furthermore, HIV-specific CD4⁺ T-cell responses were greater among animals immunized with the particle-competent vector. Using a human dendritic cell model of antigen presentation in vitro, vCP205 generated greater ELISPOT responses than Myr^– vCP205. These results demonstrate that pseudovirion particle production by live-vector HIV vaccines enhances HIV-specific cellular and humoral immune responses.

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* Corresponding author. Mailing address: Vanderbilt University School of Medicine, 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.

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Journal of Virology, May 2005, p. 5537-5547, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5537-5547.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Zhang, X., Cassis-Ghavami, F., Eller, M., Currier, J., Slike, B. M., Chen, X., Tartaglia, J., Marovich, M., Spearman, P. (2007). Direct Comparison of Antigen Production and Induction of Apoptosis by Canarypox Virus- and Modified Vaccinia Virus Ankara-Human Immunodeficiency Virus Vaccine Vectors. J. Virol. 81: 7022-7033 [Abstract] [Full Text]