Systems design and synthetic construction of influenza virus for vaccine production

Influenza is a constantly evolving global health threat that leads to substantial morbidity and mortality particularly in vulnerable populations at either end of the age spectrum. Society has responded by creating a global public-private system that involves constant surveillance, candidate virus generation, and release reagent generation linked to worldwide influenza vaccine manufacturing capabilities. It was initially recognised that influenza circulates as multiple antigenically distinct subtypes, which led to the generation of vaccines containing multiple influenza strains. The first and still current major process used for influenza vaccine production is infection of embryonated hen's eggs with influenza virus. While this approach was a true advancement, some shortcomings such as lack of vaccine match to circulating strains due to egg adaptation and production capacity limitations have led to recent innovations in mammalian cell production and synthetic technologies aimed at further improving global influenza responses.

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Population balance modeling of influenza virus replication in MDCK cells during vaccine production

Computer Aided Chemical Engineering - 18th European Symposium on Computer Aided Process Engineering ◽

10.1016/s1570-7946(08)80027-2 ◽

2008 ◽

pp. 133-138 ◽

Cited By ~ 3

Author(s):

Thomas Müller ◽

Josef Schulze-Horsel ◽

Yury Sidorenko ◽

Udo Reichi ◽

Achim Kienle

Keyword(s):

Influenza Virus ◽

Virus Replication ◽

Mdck Cells ◽

Population Balance ◽

Vaccine Production ◽

Population Balance Modeling ◽

Influenza Virus Replication

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Stochastic population balance modeling of influenza virus replication in vaccine production processes. II. Detailed description of the replication mechanism

Chemical Engineering Science ◽

10.1016/j.ces.2007.12.034 ◽

2008 ◽

Vol 63 (8) ◽

pp. 2299-2304 ◽

Cited By ~ 15

Author(s):

Y. Sidorenko ◽

A. Voigt ◽

J. Schulze-Horsel ◽

U. Reichl ◽

A. Kienle

Keyword(s):

Influenza Virus ◽

Virus Replication ◽

Population Balance ◽

Vaccine Production ◽

Population Balance Modeling ◽

Replication Mechanism ◽

Production Processes ◽

Influenza Virus Replication

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An MDCK Cell Culture-Derived Formalin-Inactivated Influenza Virus Whole-Virion Vaccine from an Influenza Virus Library Confers Cross-Protective Immunity by Intranasal Administration in Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.00024-13 ◽

2013 ◽

Vol 20 (7) ◽

pp. 998-1007 ◽

Cited By ~ 8

Author(s):

Ahmad M. Haredy ◽

Nobuyuki Takenaka ◽

Hiroshi Yamada ◽

Yoshihiro Sakoda ◽

Masatoshi Okamatsu ◽

...

Keyword(s):

Cell Culture ◽

Influenza Virus ◽

Pandemic Influenza ◽

Mdck Cell ◽

Intranasal Administration ◽

Influenza Viruses ◽

Production Model ◽

Vaccine Production ◽

Intranasal Immunization ◽

Homologous Virus

ABSTRACTIt is currently impossible to predict the next pandemic influenza virus strain. We have thus established a library of influenza viruses of all hemagglutinin and neuraminidase subtypes and their genes. In this article, we examine the applicability of a rapid production model for the preparation of vaccines against emerging pandemic influenza viruses. This procedure utilizes the influenza virus library, cell culture-based vaccine production, and intranasal administration to induce a cross-protective immune response. First, an influenza virus reassortant from the library, A/duck/Hokkaido/Vac-3/2007 (H5N1), was passaged 22 times (P22) in Madin-Darby canine kidney (MDCK) cells. The P22 virus had a titer of >2 ×108PFU/ml, which was 40 times that of the original strain, with 4 point mutations, which altered amino acids in the deduced protein sequences encoded by the PB2 and PA genes. We then produced a formalin-inactivated whole-virion vaccine from the MDCK cell-cultured A/duck/Hokkaido/Vac-3/2007 (H5N1) P22 virus. Intranasal immunization of mice with this vaccine protected them against challenges with lethal influenza viruses of homologous and heterologous subtypes. We further demonstrated that intranasal immunization with the vaccine induced cross-reactive neutralizing antibody responses against the homotypic H5N1 influenza virus and its antigenic variants and cross-reactive cell-mediated immune responses to the homologous virus, its variants within a subtype, and even an influenza virus of a different subtype. These results indicate that a rapid model for emergency vaccine production may be effective for producing the next generation of pandemic influenza virus vaccines.

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