title: Virosome-mediated delivery of protein antigens in vivo: efficient induction of class I MHC-restricted cytotoxic T lymphocyte activity.
abstract: Induction of CTL responses against protein antigens is an important aim in vaccine development. In this paper we present fusion-active virosomes as a vaccine delivery system capable of efficient induction of CTL responses in vivo. Virosomes are reconstituted viral membranes, which do not contain the genetic material of the virus they are derived from. Foreign macromolecules, including protein antigens, can be encapsulated in virosomes during the reconstitution process. Functionally reconstituted virosomes retain the cell binding and fusion characteristics of the native virus. Thus, upon uptake by cells through receptor-mediated endocytosis, virosomes will deliver their content to the cell cytosol. In a previous study, we demonstrated that protein antigens delivered in this manner to dendritic cells are efficiently processed for both MHC class I and class II presentation. Here, we studied in vivo induction of cellular immune responses against virosome-encapsulated ovalbumin (OVA) in mice. As little as 0.75 microg OVA delivered by fusion-active virosomes was sufficient to induce a powerful class I MHC-restricted CTL response. All immunization routes that were used (i.m., i.p. and s.c.) resulted in efficient induction of CTL activity. The CTLs induced were cytotoxic in a standard 51Cr-release assay and produced IFNgamma in response to OVA peptide. Thus, virosomes represent an ideal antigen delivery system for induction of cellular immunity against encapsulated protein antigens.
authors.affiliation: Department of Medical Microbiology, Molecular Virology Section, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands. l.bungener@med.rug.nl
authors.forename: Laura
authors.initials: L
authors.lastname: Bungener
authors.forename: Anke
authors.initials: A
authors.lastname: Huckriede
authors.forename: Arjan
authors.initials: A
authors.lastname: de Mare
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Vries-Idema
authors.forename: Jan
authors.initials: J
authors.lastname: Wilschut
authors.forename: Toos
authors.initials: T
authors.lastname: Daemen
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics*; D005802:Genes, MHC Class II / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010743:Phospholipids; D011506:Proteins / Q000276:immunology*; D022721:Vaccines, Virosome / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D010743:Phospholipids; D011506:Proteins; D022721:Vaccines, Virosome; D007371:Interferon-gamma; D010047:Ovalbumin