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

• Published in: Veterinary Research
• Main Authors: Cheung, Ying-Kit, Cheng, Samuel Chak-Sum, Ke, Yan, Xie, Yong
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2010
• Subjects: Influenza A virus; H5N1 nucleoprotein; HLA-A{*}0201 T-cell epitope; Single-chain trimer; HHD transgenic mouse model; 0201 T-cell epitope; HLA-A; Avian flu
• Online Access: http://repository.ust.hk/ir/Record/1783.1-17239; https://doi.org/10.1051/vetres/2009071; http://lbdiscover.ust.hk/uresolver?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rfr_id=info:sid/HKUST:SPI&rft.genre=article&rft.issn=0928-4249&rft.volume=41&rft.issue=2&rft.date=2010&rft.spage=&rft.aulast=Cheung&rft.aufirst=Ying-Kit&rft.atitle=Two+novel+HLA-A{*}0201+T-cell+epitopes+in+avian+H5N1+viral+nucleoprotein+induced+specific+immune+responses+in+HHD+mice; http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=LinksAMR&SrcApp=PARTNER_APP&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000274934800008; http://www.scopus.com/record/display.url?eid=2-s2.0-77249148325&origin=inward

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.