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Journal of Virology, February 2009, p. 1501-1510, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.02119-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Inactivated Simian Immunodeficiency Virus-Pulsed Autologous Fresh Blood Cells as an Immunotherapy Strategy{triangledown} ,{dagger}

Rosemarie D. Mason,1 Sheilajen Alcantara,1 Viv Peut,1 Liyen Loh,1 Jeffrey D. Lifson,2 Robert De Rose,1 and Stephen J. Kent1*

Department of Microbiology and Immunology, University of Melbourne, Melbourne 3010, Australia,1 AIDS and Cancer Virus Program, SAIC Frederick, Inc., National Cancer Institute, Frederick, Maryland 217922

Received 8 October 2008/ Accepted 9 November 2008

Practical immunotherapies for human immunodeficiency virus infection are needed. We evaluated inactivated simian immunodeficiency virus (SIV) pulsed onto fresh peripheral blood mononuclear cells in 12 pigtail macaques with chronic SIVmac251 infection for T-cell immunogenicity in a randomized cross-over design study. The immunotherapy was safe and convincingly induced high levels of SIV-specific CD4+ T-cell responses (mean, 5.9% ± 1.3% of all CD4+ T cells) and to a lesser extent SIV-specific CD8+ T-cell responses (mean, 0.7% ± 0.4%). Responses were primarily directed toward Gag and less frequently toward Env but not Pol or regulatory/accessory SIV proteins. T-cell responses against Gag were generally broad and polyfunctional, with a mean of 2.7 CD4+ T-cell epitopes mapped per animal and more than half of the SIV Gag-specific CD4+ T cells expressing three or more effector molecules. The immunogenicity was comparable to that found in previous studies of peptide-pulsed blood cells. Despite the high-level immunogenicity, no reduction in viral load was observed in the chronically viremic macaques. This contrasts with our studies of immunization with peptide-pulsed blood cells during early SIV infection in macaques. Future studies of inactivated virus-pulsed blood cell immunotherapy during early infection of patients receiving antiretroviral therapy are warranted.

* Correspondence author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Melbourne 3010, Australia. Phone: 61383449939. Fax: 6138343846. E-mail: skent{at}unimelb.edu.au

{triangledown} Published ahead of print on 19 November 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, February 2009, p. 1501-1510, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.02119-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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