Two novel HLA-A*0201 T-cell epitopes in avian H5N1 viral nucleoprotein induced specific immune responses in HHD mice

Vet Res. Mar-Apr 2010;41(2):24. doi: 10.1051/vetres/2009071. Epub 2009 Nov 27.

Abstract

The influenza A nucleoprotein (NP) is an attractive target for avian flu vaccine development because of its high conversancy in the evolutionary chain of the virus. Here we identified two novel HLA-A*0201 restricted NP epitopes, named H5N1 NP373-381 AMDSNTLEL (NP373) and NP458-466 FQGRGVFEL (NP458), using computational bioinformatic analysis. The NP peptides showed a high binding affinity to HLA-A*0201 on T2 cells, and were able to induce the activation of the cytotoxic T cells in the human peripheral blood mononuclear cells. We examined the potential of using NP373 and NP458 peptide sequences supplemented with a single-chain trimer as potential DNA vaccine candidates in an HHD transgenic mouse model. A gene gun delivery system was used for administrating the vaccine candidates into the animals. The results from cytotoxicity and ELISPOT assays indicated that a significant amount of IFN-gamma was secreted by the T cells of the vaccinated mice, and the T cells were able to eliminate the corresponding peptide-loaded T2 cells. The discovery of these novel immunogenic NP peptides provides valuable information for avian flu vaccine design and construction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biolistics
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A Antigens / immunology*
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / prevention & control
  • Specific Pathogen-Free Organisms
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology
  • Viral Nonstructural Proteins / immunology*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • Influenza Vaccines
  • Vaccines, DNA
  • Viral Nonstructural Proteins