title: Prior DNA immunization enhances immune response to dominant and subdominant viral epitopes induced by a fowlpox-based SIVmac vaccine in long-term slow-progressor macaques infected with SIVmac251.
abstract: A therapeutic vaccine for individuals infected with HIV-1 and treated with antiretroviral therapy (ART) should be able to replenish virus-specific CD4+ T-cells and broaden the virus-specific CD8+ T-cell response in order to maintain CD8+ T-cell function and minimize viral immune escape after ART cessation. Because a combination of DNA and recombinant poxvirus vaccine modalities induces high levels of virus-specific CD4+ T-cell response and broadens the cytolytic activity in naive macaques, we investigated whether the same results could be obtained in SIVmac251-infected macaques. The macaques studied here were long-term nonprogressors that naturally contained viremia but were nevertheless treated with a combination of antiviral drugs to assess more carefully the effect of vaccination in the context of ART. The combination of a DNA expressing the gag and pol genes (DNA-SIV-gp) of SIVmac239 followed by a recombinant fowlpox expressing the same SIVmac genes (FP-SIV-gp) was significantly more immunogenic than two immunizations of FP-SIV-gp in SIVmac251-infected macaques treated with ART. The DNA/FP combination significantly expanded and broadened Gag-specific T-cell responses measured by tetramer staining, ELISPOT, and intracellular cytokine staining and measurement of ex vivo cytolytic function. Importantly, the combination of these vaccine modalities also induced a sizeable expansion in most macaques of Gag-specific CD8-(CD4+) T-cells able to produce TNF-alpha. Hopefully, this modality of vaccine combination may be useful in the clinical management of HIV-1-infected individuals.
authors.affiliation: National Cancer Institute, Basic Research Laboratory, 41/D804, Bethesda, MD 20892-5055, USA.
authors.forename: Antonia
authors.initials: A
authors.lastname: Radaelli
authors.forename: Janos
authors.initials: J
authors.lastname: Nacsa
authors.forename: Wen Po
authors.initials: WP
authors.lastname: Tsai
authors.forename: Yvette
authors.initials: Y
authors.lastname: Edghill-Smith
authors.forename: Carlo
authors.initials: C
authors.lastname: Zanotto
authors.forename: Veronica
authors.initials: V
authors.lastname: Elli
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Tryniszewska
authors.forename: Phil
authors.initials: P
authors.lastname: Markham
authors.forename: Gail P
authors.initials: GP
authors.lastname: Mazzara
authors.forename: Dennis
authors.initials: D
authors.lastname: Panicali
authors.forename: Carlo
authors.initials: C
authors.lastname: De Giuli Morghen
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D016056:Immunodominant Epitopes / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics* / Q000502:physiology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D016056:Immunodominant Epitopes; D019444:Vaccines, DNA; D014765:Viral Vaccines