title: Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+) T cell responses in HIV-1-infected individuals.
abstract: Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+) T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+) T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+) T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.
authors.affiliation: Service of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain. nucliment@yahoo.es
authors.forename: Núria
authors.initials: N
authors.lastname: Climent
authors.forename: Susana
authors.initials: S
authors.lastname: Guerra
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: Cristina
authors.initials: C
authors.lastname: Rovira
authors.forename: Laia
authors.initials: L
authors.lastname: Miralles
authors.forename: Carmen Elena
authors.initials: CE
authors.lastname: Gómez
authors.forename: Núria
authors.initials: N
authors.lastname: Piqué
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil
authors.forename: José María
authors.initials: JM
authors.lastname: Gatell
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015752:Genes, env / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011212:Poxviridae / Q000235:genetics* / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018925:Chemokines; D016207:Cytokines; D015488:HIV Antigens