title: Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA.
abstract: The induction of anti-influenza cytotoxic T lymphocytes (CTL) in vivo by immunizing mice with liposomes containing messenger RNA (mRNA) encoding the influenza virus nucleoprotein (NP) is described. NP mRNA, obtained by in vitro transcription, was encapsulated into simple cholesterol/phosphatidylcholine/phosphatidylserine liposomes by the detergent removal technique. The dependence of the route of mRNA-liposomes delivery on CTL induction was studied. The CTL induced were identical to those obtained in vivo with infectious virus in terms of specificity, lysing both peptide-sensitized and virus-infected targets. Furthermore, with the same mRNA-liposome preparation, virus-specific CTL responses could be also elicited in mice of three different haplotypes each of them known to present a distinct NP peptide in an MHC-restricted fashion. The relevance of these results in the context of vaccine development is discussed.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U152, Marcy L'Etoile, France.
authors.forename: F
authors.initials: F
authors.lastname: Martinon
authors.forename: S
authors.initials: S
authors.lastname: Krishnan
authors.forename: G
authors.initials: G
authors.lastname: Lenzen
authors.forename: R
authors.initials: R
authors.lastname: Magné
authors.forename: E
authors.initials: E
authors.lastname: Gomard
authors.forename: J G
authors.initials: JG
authors.lastname: Guillet
authors.forename: J P
authors.initials: JP
authors.lastname: Lévy
authors.forename: P
authors.initials: P
authors.lastname: Meulien
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D007111:Immunity, Cellular; D009980:Influenza A virus / Q000276:immunology*; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008815:Mice, Inbred Strains; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D012333:RNA, Messenger / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D008081:Liposomes; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D012333:RNA, Messenger; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014765:Viral Vaccines