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      Multi-antigen avian influenza a (H7N9) virus-like particles: particulate characterizations and immunogenicity evaluation in murine and avian models

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          Abstract

          Background

          Human infection with avian influenza A virus (H7N9) was first reported in China in March 2013. Since then, hundreds of cases have been confirmed showing severe symptoms with a high mortality rate. The virus was transmitted from avian species to humans and has spread to many neighboring areas, raising serious concerns over its pandemic potential. Towards containing the disease, the goal of this study is to prepare a virus-like particle (VLP) that consists of hemagglutinin (HA), neuraminidase (NA) and matrix protein 1 (M1) derived from the human isolate A/Taiwan/S02076/2013(H7N9) for potential vaccine development.

          Results

          Full length HA, NA, and M1 protein genes were cloned and expressed using a baculoviral expression system, and the VLPs were generated by co-infecting insect cells with three respective recombinant baculoviruses. Nanoparticle tracking analysis and transmission electron microscopy were applied to verify the VLPs’ structure and antigenicity, and the multiplicity of infection of the recombinant baculoviruses was adjusted to achieve the highest hemagglutination activity. In animal experiments, BALB/c mice and specific-pathogen-free chickens receiving the VLP immunization showed elevated hemagglutination inhibition serum titer and antibodies against NA and M1 proteins. In addition, examination of cellular immunity showed the VLP-immunized mice and chickens exhibited an increased splenic antigen-specific cytokines production.

          Conclusions

          The H7N9 VLPs possess desirable immunogenicity in vivo and may serve as a candidate for vaccine development against avian influenza A (H7N9) infection.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12896-016-0321-6) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

          New England Journal of Medicine, 368(20), 1888-1897
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            Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

            New England Journal of Medicine, 370(6), 520-532
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              Influenza virus assembly and budding.

              Influenza A virus causes seasonal epidemics, sporadic pandemics and is a significant global health burden. Influenza virus is an enveloped virus that contains a segmented negative strand RNA genome. Assembly and budding of progeny influenza virions is a complex, multi-step process that occurs in lipid raft domains on the apical membrane of infected cells. The viral proteins hemagglutinin (HA) and neuraminidase (NA) are targeted to lipid rafts, causing the coalescence and enlargement of the raft domains. This clustering of HA and NA may cause a deformation of the membrane and the initiation of the virus budding event. M1 is then thought to bind to the cytoplasmic tails of HA and NA where it can then polymerize and form the interior structure of the emerging virion. M1, bound to the cytoplasmic tails of HA and NA, additionally serves as a docking site for the recruitment of the viral RNPs and may mediate the recruitment of M2 to the site of virus budding. M2 initially stabilizes the site of budding, possibly enabling the polymerization of the matrix protein and the formation of filamentous virions. Subsequently, M2 is able to alter membrane curvature at the neck of the budding virus, causing membrane scission and the release of the progeny virion. This review investigates the latest research on influenza virus budding in an attempt to provide a step-by-step analysis of the assembly and budding processes for influenza viruses. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                winnichen@ntu.edu.tw
                Journal
                BMC Biotechnol
                BMC Biotechnol
                BMC Biotechnology
                BioMed Central (London )
                1472-6750
                7 January 2017
                7 January 2017
                2017
                : 17
                : 2
                Affiliations
                [1 ]Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
                [2 ]Research Center for Nanotechnology and Infectious Diseases, Taipei, Taiwan
                [3 ]Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan
                [4 ]Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan
                [5 ]Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan
                [6 ]Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan
                Article
                321
                10.1186/s12896-016-0321-6
                5219756
                28061848
                d6afc41f-572e-4329-b533-003a1ced3957
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 June 2016
                : 7 December 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan;
                Award ID: MOST-103-2321-B-002-062
                Award ID: MOST-104-2321-B-002-020
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Biotechnology
                avian influenza virus a (h7n9),virus-like particles,vaccine
                Biotechnology
                avian influenza virus a (h7n9), virus-like particles, vaccine

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