Abstract
A cohort of rhesus macaques with long-standing SIVmac251 infection (> or =5 mo) was treated with continuous antiretroviral therapy (ART). A group of eight macaques was vaccinated with or without simultaneous administration of low dose IL-2 with the highly attenuated poxvirus vector (NYVAC) vaccine candidate expressing the SIVmac structural gag-pol-env (gpe) genes and a novel chimeric fusion protein derived from the rev-tat-nef (rtn) regulatory genes. Control groups consisted of mock-vaccinated macaques or animals treated only with IL-2. Vaccination significantly expanded both virus-specific CD4(+) and CD8(+) T cell responses, and IL-2 further increased the vaccine-induced response to an immunodominant Gag epitope. Following antiretroviral treatment interruption, the viral set point was significantly lower in vaccinated than in control macaques for at least 4 consecutive mo, and viral containment was inversely correlated with vaccine-induced, virus-specific CD4(+) and CD8(+) T cell responses. These data provide the proof of concept that therapeutic vaccination before cessation of ART may be a feasible approach in the clinical management of HIV-1 infection.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antiviral Agents / administration & dosage
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Antiviral Agents / therapeutic use*
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CD4-CD8 Ratio
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / virology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / virology
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Drug Therapy, Combination
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Epitopes, T-Lymphocyte / immunology
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Immunization Schedule
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Interleukin-2 / administration & dosage
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Interleukin-2 / therapeutic use
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Macaca mulatta
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SAIDS Vaccines / administration & dosage*
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SAIDS Vaccines / immunology*
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Simian Acquired Immunodeficiency Syndrome / drug therapy
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Simian Acquired Immunodeficiency Syndrome / immunology
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Simian Acquired Immunodeficiency Syndrome / prevention & control*
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Simian Acquired Immunodeficiency Syndrome / virology*
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Simian Immunodeficiency Virus / drug effects
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Simian Immunodeficiency Virus / immunology
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Simian Immunodeficiency Virus / physiology*
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Viremia / drug therapy
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Viremia / immunology
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Viremia / prevention & control
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Virus Replication / drug effects
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Virus Replication / immunology*
Substances
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Antiviral Agents
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Epitopes, T-Lymphocyte
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Interleukin-2
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SAIDS Vaccines