title: Mature dendritic cells infected with canarypox virus elicit strong anti-human immunodeficiency virus CD8+ and CD4+ T-cell responses from chronically infected individuals.
abstract: Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-1) sequences are promising vaccine candidates, as they replicate poorly in human cells. However, when delivered intramuscularly the vaccines have induced inconsistent and in some cases transient antigen-specific cytotoxic T-cell (CTL) responses in seronegative volunteers. An attractive way to enhance these responses would be to target canarypox virus to professional antigen-presenting cells such as dendritic cells (DCs). We studied (i) the interaction between canarypox virus and DCs and (ii) the T-cell responses induced by DCs infected with canarypox virus vectors containing HIV-1 genes. Mature and not immature DCs resisted the cytopathic effects of canarypox virus and elicited strong effector CD8+ T-cell responses from chronically infected HIV+ individuals, e.g., cytolysis, and secretion of gamma interferon (IFN-gamma) and beta-chemokines. Furthermore, canarypox virus-infected DCs were >30-fold more efficient than monocytes and induced responses that were comparable to those induced by vaccinia virus vectors or peptides. Addition of exogenous cytokines was not necessary to elicit CD8+ effector cells, although the presence of CD4+ T cells was required for their expansion and maintenance. Most strikingly, canarypox virus-infected DCs were directly able to stimulate HIV-specific, IFN-gamma-secreting CD4 helper responses from bulk as well as purified CD4+ T cells. Therefore, these results suggest that targeting canarypox virus vectors to mature DCs could potentially elicit both anti-HIV CD8+ and CD4+ helper responses in vivo.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: J
authors.initials: J
authors.lastname: Engelmayer
authors.forename: M
authors.initials: M
authors.lastname: Larsson
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: W I
authors.initials: WI
authors.lastname: Cox
authors.forename: R M
authors.initials: RM
authors.lastname: Steinman
authors.forename: N
authors.initials: N
authors.lastname: Bhardwaj
mesh_terms: D016915:AIDS Vaccines; D000328:Adult; D018150:Avipoxvirus / Q000276:immunology* / Q000472:pathogenicity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D018946:Chemokine CCL5 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011213:Poxviridae Infections / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology
chemical_list: D016915:AIDS Vaccines; D018946:Chemokine CCL5; D007371:Interferon-gamma