HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hel, Z. Articles by Franchini, G. Search for Related Content PubMed PubMed Citation Articles by Hel, Z. Articles by Franchini, G.

Improved Vaccine Protection from Simian AIDS by the Addition of Nonstructural Simian Immunodeficiency Virus Genes¹

Zdenk Hel^*,, Wen-Po Tsai^*, Elzbieta Tryniszewska^*,, Janos Nacsa^*, Phillip D. Markham, Mark G. Lewis^¶, George N. Pavlakis^||, Barbara K. Felber^#, Jim Tartaglia^** and Genoveffa Franchini^2,*

^* Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892; Department of Pathology, Center for AIDS Research, University of Alabama, Birmingham, AL 35249; Third Department of Pediatrics, Medical University of Bialystok, Waszyngtona, Poland; Advanced BioScience Laboratories, Kensington, MD 20895; ^¶ Bioqual, Rockville, MD 20850; ^|| Human Retrovirus Section and ^# Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, MD 21702; and ^** Sanofi-Pasteur, Toronto, Canada

An HIV-1 vaccine able to induce broad CD4⁺ and CD8⁺ T cell responses may provide long-term control of viral replication. In this study we directly assess the relative benefit of immunization with vaccines expressing three structural Ags (Gag, Pol, and Env), three early regulatory proteins (Rev, Tat, and Nef), or a complex vaccine expressing all six Ags. The simultaneous administration of all six Ags during vaccination resulted in Ag competition manifested by a relative reduction of CD8⁺ T cell and lymphoproliferative responses to individual Ags. Despite the Ag competition, vaccination with all six Ags resulted in a delay in the onset and a decrease in the extent of acute viremia after mucosal challenge exposure to highly pathogenic SIV_mac251. Reduced levels of acute viremia correlated with lower post-set point viremia and long-term control of infection. In immunized animals, virus-specific CD4⁺ T cell and lymphoproliferative responses were preserved during acute viremia, and the maintenance of these responses predicted the long-term virological outcome. Taken together, these results suggest that the breadth of the immune response is probably more important than high frequency responses to a limited number of epitopes. These data provide the first clear evidence of the importance of nonstructural HIV Ags as components of an HIV-1 vaccine.

This article has been cited by other articles:

				K. A. Schoenly and D. B. Weiner Human Immunodeficiency Virus Type 1 Vaccine Development: Recent Advances in the Cytotoxic T-Lymphocyte Platform "Spotty Business" J. Virol., April 1, 2008; 82(7): 3166 - 3180. [Full Text] [PDF]

				J. T. Loffredo, A. T. Bean, D. R. Beal, E. J. Leon, G. E. May, S. M. Piaskowski, J. R. Furlott, J. Reed, S. K. Musani, E. G. Rakasz, et al. Patterns of CD8+ Immunodominance May Influence the Ability of Mamu-B*08-Positive Macaques To Naturally Control Simian Immunodeficiency Virus SIVmac239 Replication J. Virol., February 15, 2008; 82(4): 1723 - 1738. [Abstract] [Full Text] [PDF]

				G. Koopman, D. Mortier, S. Hofman, N. Mathy, M. Koutsoukos, P. Ertl, P. Overend, C. van Wely, L. L. Thomsen, B. Wahren, et al. Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian human immunodeficiency virus viraemia with protein/DNA combination J. Gen. Virol., February 1, 2008; 89(2): 540 - 5533. [Abstract] [Full Text] [PDF]

				T. Demberg, R. H. Florese, M. J. Heath, K. Larsen, I. Kalisz, V. S. Kalyanaraman, E. M. Lee, R. Pal, D. Venzon, R. Grant, et al. A Replication-Competent Adenovirus-Human Immunodeficiency Virus (Ad-HIV) tat and Ad-HIV env Priming/Tat and Envelope Protein Boosting Regimen Elicits Enhanced Protective Efficacy against Simian/Human Immunodeficiency Virus SHIV89.6P Challenge in Rhesus Macaques J. Virol., April 1, 2007; 81(7): 3414 - 3427. [Abstract] [Full Text] [PDF]

				M. Pistello, F. Bonci, J. N. Flynn, P. Mazzetti, P. Isola, E. Zabogli, V. Camerini, D. Matteucci, G. Freer, P. Pelosi, et al. AIDS Vaccination Studies with an Ex Vivo Feline Immunodeficiency Virus Model: Analysis of the Accessory ORF-A Protein and DNA as Protective Immunogens. J. Virol., September 1, 2006; 80(18): 8856 - 8868. [Abstract] [Full Text] [PDF]

				N. A. Wilson, J. Reed, G. S. Napoe, S. Piaskowski, A. Szymanski, J. Furlott, E. J. Gonzalez, L. J. Yant, N. J. Maness, G. E. May, et al. Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239. J. Virol., June 1, 2006; 80(12): 5875 - 5885. [Abstract] [Full Text] [PDF]