title: Repeated DNA therapeutic vaccination of chronically SIV-infected macaques provides additional virological benefit.
abstract: We have previously reported that therapeutic immunization by intramuscular injection of optimized plasmid DNAs encoding SIV antigens effectively induces immune responses able to reduce viremia in antiretroviral therapy (ART)-treated SIVmac251-infected Indian rhesus macaques. We subjected such therapeutically immunized macaques to a second round of therapeutic vaccination using a combination of plasmids expressing SIV genes and the IL-15/IL-15 receptor alpha as molecular adjuvant, which were delivered by the more efficacious in vivo constant-current electroporation. A very strong induction of antigen-specific responses to Gag, Env, Nef, and Pol, during ART (1.2-1.6% of SIV-specific T cells in the circulating T lymphocytes) was obtained with the improved vaccination method. Immunological responses were characterized by the production of IFN-gamma, IL-2, and TNF-alpha either alone, or in combination as double or triple cytokine positive multifunctional T cells. A significant induction of CD4(+) T cell responses, mainly targeting Gag, Nef, and Pol, as well as of CD8(+) T cells, mainly targeting Env, was found in both T cells with central memory and effector memory markers. After release from ART, the animals showed a virological benefit with a further approximately 1 log reduction in viremia. Vaccination with plasmid DNAs has several advantages over other vaccine modalities, including the possibility for repeated administration, and was shown to induce potent, efficacious, and long-lasting recall immune responses. Therefore, these data support the concept of adding DNA vaccination to the HAART regimen to boost the HIV-specific immune responses.
authors.affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, United States.
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.forename: Agneta
authors.initials: A
authors.lastname: von Gegerfelt
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.forename: Georgios
authors.initials: G
authors.lastname: Miteloudis
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.forename: Cristina
authors.initials: C
authors.lastname: Bergamaschi
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jalah
authors.forename: Vainav
authors.initials: V
authors.lastname: Patel
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Draghia-Akli
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D018274:Electroporation; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D019409:Interleukin-15 / Q000276:immunology; D008253:Macaca mulatta; D010957:Plasmids; D053647:Receptors, Interleukin-15 / Q000276:immunology; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000276:immunology*; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D016207:Cytokines; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D018449:SAIDS Vaccines; D019444:Vaccines, DNA