Elsevier

Virology

Volume 348, Issue 1, 25 April 2006, Pages 200-215
Virology

DNA immunization in combination with effective antiretroviral drug therapy controls viral rebound and prevents simian AIDS after treatment is discontinued

https://doi.org/10.1016/j.virol.2005.12.008Get rights and content
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Abstract

DNA immunization in conjunction with antiretroviral therapy was evaluated in SIV-infected rhesus macaques treated with [R]-9-[2-phosphonylmethoxypropyl]adenine (PMPA). Macaques were immunized monthly with DNA vaccines expressing either SIV gag/tat or SIV gag/tat and 19 CD8+ T cell epitopes during 7 months of therapy. Half the animals from each group were additionally immunized before infection. Only 60% of the animals (4 controls, 20 vaccinated) responded to PMPA (ART responders). All 4 ART responder controls demonstrated viral rebound or CD4 decline after PMPA was withdrawn. In contrast, 17 of 20 vaccinated ART responders contained viral rebound for over 7 months after PMPA was withdrawn. Viral control correlated with stable CD4 counts, higher lymphoproliferation and an increase in the magnitude and breadth of the CD8+ T cell response. Immunizing before infection or with multi-epitopes enhanced these effects. These results demonstrate that DNA immunization during antiretroviral therapy may be an effective strategy to treat HIV infection.

Abbreviations

ART
antiretroviral therapy
HAART
highly active antiretroviral therapy
PMPA
[R]-9-[2-phosphonylmethoxypropyl]adenine
HBcAg
hepatitis B virus core antigen
PMED
particle-mediated epidermal delivery
PBMC
peripheral blood mononuclear cells
LPR
lymphoproliferative response
CTL
cytotoxic T lymphocyte

Keywords

Immunotherapy
Antiretroviral therapy
DNA vaccine
SIV AIDS

Cited by (0)

1

Current address: Department of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.

2

Current address: Chiron Corporation, Emeryville, CA, USA.

3

Current address: EMD Biosciences, Inc., Madison, WI, USA.

4

Current address: Recombiworks, Cranberry, PA, USA.

5

Current address: Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

6

Current address: Department of Biological Sciences, California State University - San Marcos, San Marcos, CA 92096, USA.

7

Current address: Ligocyte Pharmaceuticals, Inc., Bozeman, Montana, USA.