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.
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.
Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106 Magdeburg, Germany. Electronic address: pieler@mpi-magdeburg.mpg.de.
Michael M
MM
Pieler
Institute of Medical Microbiology and Hospital Hygiene, Infection Immunology Group, University Hospital of the Otto-von-Guericke University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany. Electronic address: sarah.frentzel@med.ovgu.de.
Sarah
S
Frentzel
Institute of Medical Microbiology and Hospital Hygiene, Infection Immunology Group, University Hospital of the Otto-von-Guericke University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany; Helmholtz Centre for Infection Research, Immune Regulation Group, Inhoffenstraße 7, 38124 Braunschweig, Germany. Electronic address: dunja.bruder@med.ovgu.de.
Dunja
D
Bruder
Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106 Magdeburg, Germany; Otto-von-Guericke University Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: mwolff@mpi-magdeburg.mpg.de.
Michael W
MW
Wolff
Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106 Magdeburg, Germany; Otto-von-Guericke University Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: ureichl@mpi-magdeburg.mpg.de.
Udo
U
Reichl
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002482:Cellulose; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D009980:Influenza A virus / Q000254:growth & development* / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D008280:Magnetics; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D016019:Survival Analysis; D013678:Technology, Pharmaceutical / Q000379:methods*; D016896:Treatment Outcome; D014776:Virus Cultivation / Q000379:methods*
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D002482:Cellulose
Formulation; Immunization; Influenza; Magnetic particles; Purification; Vaccination