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 All 4 ART responder controls demonstrated viral rebound or CD4 decline after PMPA was withdrawn. In contrast, 17 of 20 vaccinated ART responders contained viral rebound for over 7 months after PMPA was withdrawn.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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenine / administration & dosage
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Adenine / analogs & derivatives*
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Adenine / therapeutic use
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Animals
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Anti-HIV Agents / administration & dosage
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Anti-HIV Agents / therapeutic use
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CD4 Lymphocyte Count
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CD8-Positive T-Lymphocytes / immunology
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Cell Proliferation
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Disease Progression
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology
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Gene Products, gag / genetics
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Gene Products, gag / immunology
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Gene Products, tat / genetics
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Gene Products, tat / immunology
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Immunotherapy, Active / methods
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Macaca mulatta
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Organophosphonates / administration & dosage*
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Organophosphonates / therapeutic use
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RNA, Viral / blood
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Simian Acquired Immunodeficiency Syndrome / drug therapy*
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Simian Acquired Immunodeficiency Syndrome / immunology*
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Simian Immunodeficiency Virus / drug effects
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Simian Immunodeficiency Virus / immunology*
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Statistics as Topic
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Tenofovir
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Vaccines, DNA / administration & dosage*
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Vaccines, DNA / immunology
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Viremia / prevention & control*
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Withholding Treatment
Substances
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Anti-HIV Agents
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Epitopes, T-Lymphocyte
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Gene Products, gag
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Gene Products, tat
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Organophosphonates
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RNA, Viral
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Vaccines, DNA
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Tenofovir
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Adenine