Influenza T-cell epitope-loaded virosomes adjuvanted with CpG as a potential influenza vaccine

Pharm Res. 2015 Apr;32(4):1505-15. doi: 10.1007/s11095-014-1556-3. Epub 2014 Oct 25.


Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemistry*
  • Animals
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology*
  • Humans
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / chemistry
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oligodeoxyribonucleotides / chemistry*
  • Peptide Fragments / immunology
  • Vaccines, Virosome / administration & dosage
  • Vaccines, Virosome / chemistry
  • Viral Matrix Proteins / immunology
  • Virosomes


  • Adjuvants, Immunologic
  • CpG ODN 1826
  • Epitopes, T-Lymphocyte
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Influenza Vaccines
  • M1 protein, Influenza A virus
  • Oligodeoxyribonucleotides
  • Peptide Fragments
  • Vaccines, Virosome
  • Viral Matrix Proteins
  • Virosomes