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


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          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-γ 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.

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          Heterologous protection against influenza by injection of DNA encoding a viral protein.

          Cytotoxic T lymphocytes (CTLs) specific for conserved viral antigens can respond to different strains of virus, in contrast to antibodies, which are generally strain-specific. The generation of such CTLs in vivo usually requires endogenous expression of the antigen, as occurs in the case of virus infection. To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleoprotein was injected into the quadriceps of BALB/c mice. This resulted in the generation of nucleoprotein-specific CTLs and protection from a subsequent challenge with a heterologous strain of influenza A virus, as measured by decreased viral lung titers, inhibition of mass loss, and increased survival.
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            Summary Although most influenza infections are self-limited, few other diseases exert such a huge toll of suffering and economic loss. Despite the importance of influenza, there had been, until recently, little advance in its control since amantadine was licensed almost 40 years ago. During the past decade, evidence has accrued on the protection afforded by inactivated vaccines and the safety and efficacy in children of live influenza-virus vaccines. There have been many new developments in vaccine technology. Moreover, work on viral neuraminidase has led to the licensing of potent selective antiviral drugs, and economic decision modelling provides further justification for annual vaccination and a framework for the use of neuraminidase inhibitors. Progress has also been made on developing near-patient testing for influenza that may assist individual diagnosis or the recognition of widespread virus circulation, and so optimise clinical management. Despite these advances, the occurrence of avian H5N1, H9N2, and H7N7 influenza in human beings and the rapid global spread of severe acute respiratory syndrome are reminders of our vulnerability to an emerging pandemic. The contrast between recent cases of H5N1 infection, associated with high mortality, and the typically mild, self-limiting nature of human infections with avian H7N7 and H9N2 influenza shows the gaps in our understanding of molecular correlates of pathogenicity and underlines the need for continuing international research into pandemic influenza. Improvements in animal and human surveillance, new approaches to vaccination, and increasing use of vaccines and antiviral drugs to combat annual influenza outbreaks are essential to reduce the global toll of pandemic and interpandemic influenza.
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              Mechanisms of MHC class I-restricted antigen processing and cross-presentation.

              In this review, we discuss recent data from our laboratory that address two aspects of major histocompatibility complex (MHC) class I-restricted antigen processing. First, we consider the nature of the peptide-loading complex, which is the assembly of proteins in the endoplasmic reticulum (ER) into which newly synthesized MHC class I-beta(2) microglobulin (beta(2)m) heterodimers are incorporated, and the mechanisms involved in MHC class I assembly and peptide loading that are facilitated by the peptide-loading complex. Second, we discuss mechanisms of cross-presentation, the phenomenon whereby extracellular and luminal protein antigens can be processed by antigen-presenting cells, particularly dendritic cells, and presented by MHC class I molecules to CD8(+) T cells. The focus of the discussion is mainly on the human MHC class I system.

                Author and article information

                Vet Res
                Veterinary Research
                EDP Sciences
                27 November 2009
                Mar-Apr 2010
                : 41
                : 2 ( publisher-idID: vetres/2010/02 )
                : 24
                Department of Biology, The Hong Kong University of Science and Technology Clear Water Bay, Kowloon Hong Kong SAR Republic of China
                Author notes
                [* ]Corresponding author: boyxie@ 123456ust.hk
                v09477 10.1051/vetres/2009071
                © INRA, EDP Sciences, 2010
                : 01 August 2009
                : 25 November 2009
                Page count
                Figures: 4, Tables: 1, Equations: 1, References: 29, Pages: 13
                Original Article

                Veterinary medicine
                hhd transgenic mouse model,hla-a*0201 t-cell epitope,influenza a virus,h5n1 nucleoprotein,single-chain trimer


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