title: HIV gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response.
abstract: Dendritic cells (DC) are the major APCs involved in naive T cell activation making them prime targets of vaccine research. We observed that mRNA was efficiently transfected, resulting in superior translation in DC compared with other professional APCs. A single stimulation of T cells by HIV gag-encoded mRNA-transfected DC in vitro resulted in primary CD4(+) and CD8(+) T cell immune responses at frequencies of Ag-specific cells (5-12.5%) similar to primary immune responses observed in vivo in murine models. Additionally, mRNA transfection also delivered a maturation signal to DC. Our results demonstrated that mRNA-mediated delivery of encoded Ag to DC induced potent primary T cell responses in vitro. mRNA transfection of DC, which mediated efficient delivery of antigenic peptides to MHC class I and II molecules, as well as delivering a maturation signal to DC, has the potential to be a potent and effective anti-HIV T cell-activating vaccine.
authors.affiliation: Division of. Infectious Diseases and Neurosurgery, University of Pennsylvania, Philadelphia, PA 19096, USA. dreww@mail.med.upenn.edu
authors.forename: D
authors.initials: D
authors.lastname: Weissman
authors.forename: H
authors.initials: H
authors.lastname: Ni
authors.forename: D
authors.initials: D
authors.lastname: Scales
authors.forename: A
authors.initials: A
authors.lastname: Dude
authors.forename: J
authors.initials: J
authors.lastname: Capodici
authors.forename: K
authors.initials: K
authors.lastname: McGibney
authors.forename: A
authors.initials: A
authors.lastname: Abdool
authors.forename: S N
authors.initials: SN
authors.lastname: Isaacs
authors.forename: G
authors.initials: G
authors.lastname: Cannon
authors.forename: K
authors.initials: K
authors.lastname: Karikó
mesh_terms: D017951:Antigen Presentation / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter / Q000276:immunology; D006678:HIV / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
chemical_list: D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D012367:RNA, Viral