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 Patterson, L. J.
Right arrow Articles by Robert-Guroff, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Patterson, L. J.
Right arrow Articles by Robert-Guroff, M.

Next Article 

Journal of Virology, August 2003, p. 8607-8620, Vol. 77, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.16.8607-8620.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Potent, Persistent Induction and Modulation of Cellular Immune Responses in Rhesus Macaques Primed with Ad5hr-Simian Immunodeficiency Virus (SIV) env/rev, gag, and/or nef Vaccines and Boosted with SIV gp120

L. Jean Patterson,1 Nina Malkevitch,1 Joel Pinczewski,1 David Venzon,2 Yuanmei Lou,1,{dagger} Bo Peng,1 Cindy Munch,1 Melissa Leonard,1 Ersell Richardson,1 Kristine Aldrich,1 V. S. Kalyanaraman,3 George N. Pavlakis,4 and Marjorie Robert-Guroff1*

Basic Research Laboratory,1 Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland 20892,2 National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702,4 Advanced BioScience Laboratories, Inc., Kensington, Maryland 208953

Received 24 January 2003/ Accepted 21 May 2003

Immunity elicited by multicomponent vaccines delivered by replication-competent Ad5hr-simian immunodeficiency virus (SIV) recombinants was systematically investigated. Rhesus macaques were immunized mucosally at weeks 0 and 12 with Ad5hr-SIVsmH4 env/rev, with or without Ad5hr-SIVmac239 gag or Ad5hr-SIVmac239 nef, or with all three recombinants. The total Ad5hr dosage was comparably adjusted among all animals with empty Ad5hr-{Delta}E3 vector. The macaques were boosted with SIV gp120 in monophosphoryl A-stable emulsion adjuvant at 24 and 36 weeks. Controls received Ad5hr-{Delta}E3 vector or adjuvant only. By ELISPOT analysis, all four SIV gene products elicited potent cellular immune responses that persisted 42 weeks post-initial immunization. Unexpectedly, modulation of this cellular immune response was observed among macaques receiving one, two, or three Ad5hr-SIV recombinants. Env responses were significantly enhanced throughout the immunization period in macaques immunized with Ad5hr-SIV env/rev plus Ad5hr-SIV gag and tended to be higher in macaques that also received Ad5hr-SIV nef. Macaques primed with all three recombinants displayed significant down-modulation in numbers of gamma interferon (IFN-{gamma})-secreting cells specific for SIV Nef, and the Env- and Gag-specific responses were also diminished. Modulation of antibody responses was not observed. Down-modulation was seen only during the period of Ad5hr-recombinant priming, not during subunit boosting, although SIV-specific IFN-{gamma}-secreting cells persisted. The effect was not attributable to Ad5hr replication differences among immunization groups. Vaccine delivery via replication-competent live vectors, which can persistently infect new cells and continuously present low-level antigen, may be advantageous in overcoming competition among complex immunogens for immune recognition. Effects of current multicomponent vaccines on individual immune responses should be evaluated with regard to future vaccine design.

* Corresponding author. Mailing address: NCI, NIH, 41 Library Dr. MSC5055, Building 41, Room D804, Bethesda, MD 20892-5055. Phone: (301) 496-2114. Fax: (301) 496-8394. E-mail: guroffm{at}exchange.nih.gov.

{dagger} Present address: University of British Columbia, Vancouver, BC, V6T 1X7 Canada.

Journal of Virology, August 2003, p. 8607-8620, Vol. 77, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.16.8607-8620.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Florese, R. H., Demberg, T., Xiao, P., Kuller, L., Larsen, K., Summers, L. E., Venzon, D., Cafaro, A., Ensoli, B., Robert-Guroff, M. (2009). Contribution of Nonneutralizing Vaccine-Elicited Antibody Activities to Improved Protective Efficacy in Rhesus Macaques Immunized with Tat/Env Compared with Multigenic Vaccines. J. Immunol. 182: 3718-3727 [Abstract] [Full Text]  
  • Hidajat, R., Xiao, P., Zhou, Q., Venzon, D., Summers, L. E., Kalyanaraman, V. S., Montefiori, D. C., Robert-Guroff, M. (2009). Correlation of Vaccine-Elicited Systemic and Mucosal Nonneutralizing Antibody Activities with Reduced Acute Viremia following Intrarectal Simian Immunodeficiency Virus SIVmac251 Challenge of Rhesus Macaques. J. Virol. 83: 791-801 [Abstract] [Full Text]  
  • Demberg, T., Boyer, J. D., Malkevich, N., Patterson, L. J., Venzon, D., Summers, E. L., Kalisz, I., Kalyanaraman, V. S., Lee, E. M., Weiner, D. B., Robert-Guroff, M. (2008). Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIVmac251 Mucosal Challenge. J. Virol. 82: 10911-10921 [Abstract] [Full Text]  
  • Demberg, T., Florese, R. H., Heath, M. J., Larsen, K., Kalisz, I., Kalyanaraman, V. S., Lee, E. M., Pal, R., Venzon, D., Grant, R., Patterson, L. J., Korioth-Schmitz, B., Buzby, A., Dombagoda, D., Montefiori, D. C., Letvin, N. L., Cafaro, A., Ensoli, B., Robert-Guroff, M. (2007). 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. 81: 3414-3427 [Abstract] [Full Text]  
  • Santosuosso, M., McCormick, S., Roediger, E., Zhang, X., Zganiacz, A., Lichty, B. D., Xing, Z. (2007). Mucosal Luminal Manipulation of T Cell Geography Switches on Protective Efficacy by Otherwise Ineffective Parenteral Genetic Immunization. J. Immunol. 178: 2387-2395 [Abstract] [Full Text]  
  • Florese, R. H., Van Rompay, K. K. A., Aldrich, K., Forthal, D. N., Landucci, G., Mahalanabis, M., Haigwood, N., Venzon, D., Kalyanaraman, V. S., Marthas, M. L., Robert-Guroff, M. (2006). Evaluation of Passively Transferred, Nonneutralizing Antibody-Dependent Cellular Cytotoxicity-Mediating IgG in Protection of Neonatal Rhesus Macaques against Oral SIVmac251 Challenge. J. Immunol. 177: 4028-4036 [Abstract] [Full Text]  
  • Peng, B., Wang, L. R., Gomez-Roman, V. R., Davis-Warren, A., Montefiori, D. C., Kalyanaraman, V. S., Venzon, D., Zhao, J., Kan, E., Rowell, T. J., Murthy, K. K., Srivastava, I., Barnett, S. W., Robert-Guroff, M. (2005). Replicating Rather than Nonreplicating Adenovirus-Human Immunodeficiency Virus Recombinant Vaccines Are Better at Eliciting Potent Cellular Immunity and Priming High-Titer Antibodies. J. Virol. 79: 10200-10209 [Abstract] [Full Text]  
  • Gomez-Roman, V. R., Patterson, L. J., Venzon, D., Liewehr, D., Aldrich, K., Florese, R., Robert-Guroff, M. (2005). Vaccine-Elicited Antibodies Mediate Antibody-Dependent Cellular Cytotoxicity Correlated with Significantly Reduced Acute Viremia in Rhesus Macaques Challenged with SIVmac251. J. Immunol. 174: 2185-2189 [Abstract] [Full Text]  
  • Patterson, L. J., Malkevitch, N., Venzon, D., Pinczewski, J., Gomez-Roman, V. R., Wang, L., Kalyanaraman, V. S., Markham, P. D., Robey, F. A., Robert-Guroff, M. (2004). Protection against Mucosal Simian Immunodeficiency Virus SIVmac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting. J. Virol. 78: 2212-2221 [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»