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    A cell culture-derived whole virus influenza A vaccine based on magnetic sulfated cellulose particles confers protection in mice against lethal influenza A virus infection.

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    Authors
    Pieler, Michael M
    Frentzel, Sarah
    Bruder, Dunja cc
    Wolff, Michael W
    Reichl, Udo
    Issue Date
    2016-12-07
    
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    Abstract
    Downstream processing and formulation of viral vaccines employs a large number of different unit operations to achieve the desired product qualities. The complexity of individual process steps involved, the need for time consuming studies towards the optimization of virus yields, and very high requirements regarding potency and safety of vaccines results typically in long lead times for the establishment of new processes. To overcome such obstacles, to enable fast screening of potential vaccine candidates, and to explore options for production of low cost veterinary vaccines a new platform for whole virus particle purification and formulation based on magnetic particles has been established. Proof of concept was carried out with influenza A virus particles produced in suspension Madin Darby canine kidney (MDCK) cells. The clarified, inactivated, concentrated, and diafiltered virus particles were bound to magnetic sulfated cellulose particles (MSCP), and directly injected into mice for immunization including positive and negative controls. We show here, that in contrast to the mock-immunized group, vaccination of mice with antigen-loaded MSCP (aMSCP) resulted in high anti-influenza A antibody responses and full protection against a lethal challenge with replication competent influenza A virus. Antiviral protection correlated with a 400-fold reduced number of influenza nucleoprotein gene copies in the lungs of aMSCP immunized mice compared to mock-treated animals, indicating the efficient induction of antiviral immunity by this novel approach. Thus, our data proved the use of MSCP for purification and formulation of the influenza vaccine to be fast and efficient, and to confer protection of mice against influenza A virus infection. Furthermore, the method proposed has the potential for fast purification of virus particles directly from bioreactor harvests with a minimum number of process steps towards formulation of low-cost veterinary vaccines, and for screening studies requiring fast purification protocols.
    Citation
    A cell culture-derived whole virus influenza A vaccine based on magnetic sulfated cellulose particles confers protection in mice against lethal influenza A virus infection. 2016, 34 (50):6367-6374 Vaccine
    Affiliation
    Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
    Journal
    Vaccine
    URI
    http://hdl.handle.net/10033/620738
    DOI
    10.1016/j.vaccine.2016.10.041
    PubMed ID
    27816372
    Type
    Article
    Language
    en
    ISSN
    1873-2518
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.vaccine.2016.10.041
    Scopus Count
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    publications of the work group immunoregulation (IREG)

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