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      Influenza Virus Like Particles (VLPs): Opportunities for H7N9 Vaccine Development

      review-article
      * ,
      Viruses
      MDPI
      H7N9, pandemic influenza A, avian flu, IAV, VLP vaccine

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          Abstract

          In the midst of the ongoing COVID-19 coronavirus pandemic, influenza virus remains a major threat to public health due to its potential to cause epidemics and pandemics with significant human mortality. Cases of H7N9 human infections emerged in eastern China in 2013 and immediately raised pandemic concerns as historically, pandemics were caused by the introduction of new subtypes into immunologically naïve human populations. Highly pathogenic H7N9 cases with severe disease were reported recently, indicating the continuing public health threat and the need for a prophylactic vaccine. Here we review the development of recombinant influenza virus-like particles (VLPs) as vaccines against H7N9 virus. Several approaches to vaccine development are reviewed including the expression of VLPs in mammalian, plant and insect cell expression systems. Although considerable progress has been achieved, including demonstration of safety and immunogenicity of H7N9 VLPs in the human clinical trials, the remaining challenges need to be addressed. These challenges include improvements to the manufacturing processes, as well as enhancements to immunogenicity in order to elicit protective immunity to multiple variants and subtypes of influenza virus.

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          Most cited references103

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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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            Influenza virus pleiomorphy characterized by cryoelectron tomography.

            Influenza virus remains a global health threat, with millions of infections annually and the impending threat that a strain of avian influenza may develop into a human pandemic. Despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. Pleiomorphy has thwarted structural analysis by image reconstruction of electron micrographs based on averaging many identical particles. In this study, we used cryoelectron tomography to visualize the 3D structures of 110 individual virions of the X-31 (H3N2) strain of influenza A. The tomograms distinguish two kinds of glycoprotein spikes [hemagglutinin (HA) and neuraminidase (NA)] in the viral envelope, resolve the matrix protein layer lining the envelope, and depict internal configurations of ribonucleoprotein (RNP) complexes. They also reveal the stems that link the glycoprotein ectodomains to the membrane and interactions among the glycoproteins, the matrix, and the RNPs that presumably control the budding of nascent virions from host cells. Five classes of virions, four spherical and one elongated, are distinguished by features of their matrix layer and RNP organization. Some virions have substantial gaps in their matrix layer ("molecular fontanels"), and others appear to lack a matrix layer entirely, suggesting the existence of an alternative budding pathway in which matrix protein is minimally involved.
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              The influence of antigen organization on B cell responsiveness.

              The influence of antigen epitope density and order on B cell induction and antibody production was assessed with the glycoprotein of vesicular stomatitis virus serotype Indiana [VSV-G (IND)]. VSV-G (IND) can be found in a highly repetitive form the envelope of VSV-IND and in a poorly organized form on the surface of infected cells. In VSV-G (IND) transgenic mice, B cells were unresponsive to the poorly organized VSV-G (IND) present as self antigen but responded promptly to the same antigen presented in the highly organized form. Thus, antigen organization influences B cell tolerance.

                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                08 May 2020
                May 2020
                : 12
                : 5
                : 518
                Affiliations
                Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA; itretyakova@ 123456medigen-usa.com
                Author notes
                Article
                viruses-12-00518
                10.3390/v12050518
                7291233
                32397182
                b225b15c-ad23-4d73-a49f-170e34a7f7f4
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 April 2020
                : 27 April 2020
                Categories
                Review

                Microbiology & Virology
                h7n9,pandemic influenza a,avian flu,iav,vlp vaccine
                Microbiology & Virology
                h7n9, pandemic influenza a, avian flu, iav, vlp vaccine

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