title: Transduction of human antigen-presenting cells with integrase-defective lentiviral vector enables functional expansion of primed antigen-specific CD8(+) T cells.
abstract: Nonintegrating lentiviral vectors are being developed as a efficient and safe delivery system for both gene therapy and vaccine purposes. Several reports have demonstrated that a single immunization with integration-defective lentiviral vectors (IDLVs) delivering viral or tumor model antigens in mice was able to elicit broad and long-lasting specific immune responses in the absence of vector integration. At present, no evidence has been reported showing that IDLVs are able to expand preexisting immune responses in the human context. In the present study, we demonstrate that infection of human antigen-presenting cells (APCs), such as monocyte-derived dendritic cells (DCs) and macrophages with IDLVs expressing influenza matrix M1 protein resulted in effective induction of in vitro expansion of M1-primed CD8(+) T cells, as evaluated by both pentamer staining and cytokine production. This is the first demonstration that IDLVs represent an efficient delivery system for gene transfer and expression in human APCs, useful for immunotherapeutic applications.
authors.affiliation: Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy. donatella.negri@iss.it
authors.forename: Donatella R M
authors.initials: DR
authors.lastname: Negri
authors.forename: Roberta
authors.initials: R
authors.lastname: Bona
authors.forename: Zuleika
authors.initials: Z
authors.lastname: Michelini
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Leone
authors.forename: Iole
authors.initials: I
authors.lastname: Macchia
authors.forename: Mary E
authors.initials: ME
authors.lastname: Klotman
authors.forename: Mirella
authors.initials: M
authors.lastname: Salvatore
authors.forename: Andrea
authors.initials: A
authors.lastname: Cara
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D003713:Dendritic Cells / Q000276:immunology; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007114:Immunization; D019426:Integrases / Q000235:genetics / Q000276:immunology; D016086:Lentivirus / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D014161:Transduction, Genetic; D014764:Viral Proteins / Q000276:immunology
chemical_list: D014764:Viral Proteins; D019426:Integrases