INDUCTION OF VIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN-VIVO BY LIPOSOME-ENTRAPPED MESSENGER-RNA

The induction of anti-influenza cytotoxic T lymphocytes (CTL) in vivo by immunizing mice with liposomes containing messenger RNA (mRNA) enco ding the influenza virus nucleoprotein (NP) is described. NP mRNA, obt ained by in vitro transcription, was encapsulated into simple choleste rol/phosphatidylcholine/phosphatidylserine liposomes by the detergent removal technique. The dependance of the route of mRNA-liposomes deliv ery on CTL induction was studied. The CTL induced were identical to th ose obtained in vivo with infectious virus in terms of specificity, ly sing 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 t hem known to present a distinct NP peptide in an MHC-restricted fashio n. The relevance of these results in the context of vaccine developmen t is discussed.