title: Influenza T-cell epitope-loaded virosomes adjuvanted with CpG as a potential influenza vaccine.
abstract: OBJECTIVE
  Influenza CD8(+) T-cell epitopes are conserved amongst influenza strains and can be recognized by influenza-specific cytotoxic T-cells (CTLs), which can rapidly clear infected cells. An influenza peptide vaccine that elicits these CTLs would therefore be an alternative to current influenza vaccines, which are not cross-reactive. However, peptide antigens are poorly immunogenic due to lack of delivery to antigen presenting cells, and therefore need additional formulation with a suitable delivery system. In this study, the potential of virosomes as a delivery system for an influenza T-cell peptide was investigated.
  
  
  METHODS
  The conserved human HLA-A2.1 influenza T-cell epitope M158-66 was formulated with virosomes. The immunogenicity and protective effect of the peptide-loaded virosomes was assessed in HLA-A2 transgenic mice. Delivery properties of the virosomes were studied in mice and in in vitro dendritic cell cultures.
  
  
  RESULTS
  Immunization of HLA-A2.1 transgenic C57BL/6 mice with peptide-loaded virosomes in the presence of the adjuvant CpG-ODN 1826 increased the number of peptide-specific CTLs. Vaccination with adjuvanted peptide-loaded virosomes reduced weight loss in mice after heterologous influenza infection. Association with fusion-active virosomes was found to be crucial for antigen uptake by dendritic cells, and subsequent induction of CTLs in mice.
  
  
  CONCLUSIONS
  These results show that influenza virosomes loaded with conserved influenza epitopes could be the basis of a novel cross-protective influenza vaccine.
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven, The Netherlands, peter.soema@intravacc.nl.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Soema
authors.forename: Sietske K
authors.initials: SK
authors.lastname: Rosendahl Huber
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Willems
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.forename: Gideon F A
authors.initials: GF
authors.lastname: Kersten
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Amorij
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010446:Peptide Fragments / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000737:chemistry; D014763:Viral Matrix Proteins / Q000276:immunology; D022701:Virosomes
chemical_list: D000276:Adjuvants, Immunologic; C423449:CpG ODN 1826; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D022721:Vaccines, Virosome; D014763:Viral Matrix Proteins; D022701:Virosomes