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Accelerated mass production of influenza virus seed stocks in HEK-293 suspension cell cultures by reverse genetics

Identifieur interne : 000036 ( Hal/Curation ); précédent : 000035; suivant : 000037

Accelerated mass production of influenza virus seed stocks in HEK-293 suspension cell cultures by reverse genetics

Auteurs : Ernest Milián [Canada] ; Thomas Julien [France] ; Rafael Biaggio [Canada] ; Alina Venereo-Sanchez [Canada] ; Johnny Montes [Canada] ; Aziza P. Manceur [Canada] ; Sven Ansorge [Canada] ; Emma Petiot [France] ; Manuel Rosa-Calatrava [France] ; Amine Kamen [Canada]

Source :

RBID : Hal:hal-01908853

English descriptors

Abstract

Despite major advances in developing capacities and alternative technologies to egg-based production of influenza vaccines, responsiveness to an influenza pandemic threat is limited by the time it takes to generate a Candidate Vaccine Virus (CVV) as reported by the 2015 WHO Informal Consultation report titled "Influenza Vaccine Response during the Start of a Pandemic". In previous work, we have shown that HEK-293 cell culture in suspension and serum free medium is an efficient production platform for cell culture manufacturing of influenza candidate vaccines. This report, took advantage of, recombinant DNA technology using Reverse Genetics of influenza strains, and advances in the large-scale transfection of suspension cultured HEK-293 cells. We demonstrate the efficient generation of H1N1 with the PR8 backbone reassortant under controlled bioreactor conditions in two sequential steps (transfection/rescue and infection/production). This approach could deliver a CVV for influenza vaccine manufacturing within two-weeks, starting from HA and NA pandemic sequences. Furthermore, the scalability of the transfection technology combined with the HEK-293 platform has been extensively demonstrated at \textgreater100L scale for several biologics, including recombinant viruses. Thus, this innovative approach is better suited to rationally engineer and mass produce influenza CVV within significantly shorter timelines to enable an effective global response in pandemic situations.


Url:
DOI: 10.1016/j.vaccine.2017.04.065

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Hal:hal-01908853

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<idno type="DOI">10.1016/j.vaccine.2017.04.065</idno>
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<term>Bioreactors</term>
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<term>HEK293 Cells</term>
<term>Hemagglutination Inhibition Tests</term>
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<term>Influenza A Virus</term>
<term>Influenza Vaccines</term>
<term>Influenza virus</term>
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<term>Pandemic</term>
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<term>Reverse Genetics</term>
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<p>Despite major advances in developing capacities and alternative technologies to egg-based production of influenza vaccines, responsiveness to an influenza pandemic threat is limited by the time it takes to generate a Candidate Vaccine Virus (CVV) as reported by the 2015 WHO Informal Consultation report titled "Influenza Vaccine Response during the Start of a Pandemic". In previous work, we have shown that HEK-293 cell culture in suspension and serum free medium is an efficient production platform for cell culture manufacturing of influenza candidate vaccines. This report, took advantage of, recombinant DNA technology using Reverse Genetics of influenza strains, and advances in the large-scale transfection of suspension cultured HEK-293 cells. We demonstrate the efficient generation of H1N1 with the PR8 backbone reassortant under controlled bioreactor conditions in two sequential steps (transfection/rescue and infection/production). This approach could deliver a CVV for influenza vaccine manufacturing within two-weeks, starting from HA and NA pandemic sequences. Furthermore, the scalability of the transfection technology combined with the HEK-293 platform has been extensively demonstrated at \textgreater100L scale for several biologics, including recombinant viruses. Thus, this innovative approach is better suited to rationally engineer and mass produce influenza CVV within significantly shorter timelines to enable an effective global response in pandemic situations.</p>
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<forename type="first">Aziza P.</forename>
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<idno type="stamp" n="UNIV-LYON1">Université Claude Bernard - Lyon I</idno>
<idno type="stamp" n="CIRI" corresp="UNIV-LYON1">Centre International de Recherche en Infectiologie</idno>
<idno type="stamp" n="VIRPATH-CIRI" corresp="CIRI">Virpath-CIRI- Grippe, de l'émergence au contrôle-Virpath-CIRI- Influenza, from emergence to control?</idno>
<idno type="stamp" n="ENS-LYON">École Normale Supérieure de Lyon</idno>
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<title xml:lang="en">Accelerated mass production of influenza virus seed stocks in HEK-293 suspension cell cultures by reverse genetics</title>
<author role="aut">
<persName>
<forename type="first">Ernest</forename>
<surname>Milián</surname>
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<affiliation ref="#struct-303485"></affiliation>
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<persName>
<forename type="first">Thomas</forename>
<surname>Julien</surname>
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<affiliation ref="#struct-543794"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Rafael</forename>
<surname>Biaggio</surname>
</persName>
<idno type="halauthorid">11306737</idno>
<affiliation ref="#struct-134741"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Alina</forename>
<surname>Venereo-Sanchez</surname>
</persName>
<idno type="halauthorid">11306738</idno>
<affiliation ref="#struct-303485"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Johnny</forename>
<surname>Montes</surname>
</persName>
<idno type="halauthorid">11306739</idno>
<affiliation ref="#struct-303485"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Aziza P.</forename>
<surname>Manceur</surname>
</persName>
<idno type="halauthorid">11306740</idno>
<affiliation ref="#struct-303485"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Sven</forename>
<surname>Ansorge</surname>
</persName>
<idno type="halauthorid">11306741</idno>
<affiliation ref="#struct-303485"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Emma</forename>
<surname>Petiot</surname>
</persName>
<idno type="halauthorid">11162563</idno>
<affiliation ref="#struct-543794"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Manuel</forename>
<surname>Rosa-Calatrava</surname>
</persName>
<idno type="halauthorid">412451</idno>
<affiliation ref="#struct-543794"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Amine</forename>
<surname>Kamen</surname>
</persName>
<idno type="halauthorid">1070700</idno>
<affiliation ref="#struct-134741"></affiliation>
<affiliation ref="#struct-303485"></affiliation>
</author>
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<idno type="halJournalId" status="INCOMING">107046</idno>
<title level="j">Vaccine</title>
<imprint>
<biblScope unit="volume">35</biblScope>
<biblScope unit="issue">26</biblScope>
<biblScope unit="pp">3423-3430</biblScope>
<date type="datePub">2017</date>
</imprint>
</monogr>
<idno type="doi">10.1016/j.vaccine.2017.04.065</idno>
<idno type="pubmed">28495315</idno>
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<langUsage>
<language ident="en">English</language>
</langUsage>
<textClass>
<keywords scheme="author">
<term xml:lang="en">Reverse Genetics</term>
<term xml:lang="en">Suspension cell culture</term>
<term xml:lang="en">Reassortant Viruses</term>
<term xml:lang="en">Pandemic</term>
<term xml:lang="en">Bioreactors</term>
<term xml:lang="en">Candidate Vaccine Virus (CVV)</term>
<term xml:lang="en">HEK293 Cells</term>
<term xml:lang="en">Hemagglutination Inhibition Tests</term>
<term xml:lang="en">Humans</term>
<term xml:lang="en">Influenza A Virus</term>
<term xml:lang="en">H1N1 Subtype</term>
<term xml:lang="en">Influenza Vaccines</term>
<term xml:lang="en">Influenza virus</term>
<term xml:lang="en">Large-scale</term>
<term xml:lang="en">Transfection</term>
<term xml:lang="en">Transient transfection</term>
<term xml:lang="en">Vaccines</term>
<term xml:lang="en">Virus Cultivation</term>
</keywords>
<classCode scheme="halDomain" n="sdv.imm">Life Sciences [q-bio]/Immunology</classCode>
<classCode scheme="halDomain" n="sdv.mp.bac">Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology</classCode>
<classCode scheme="halDomain" n="sdv.mp.vir">Life Sciences [q-bio]/Microbiology and Parasitology/Virology</classCode>
<classCode scheme="halTypology" n="ART">Journal articles</classCode>
</textClass>
<abstract xml:lang="en">
<p>Despite major advances in developing capacities and alternative technologies to egg-based production of influenza vaccines, responsiveness to an influenza pandemic threat is limited by the time it takes to generate a Candidate Vaccine Virus (CVV) as reported by the 2015 WHO Informal Consultation report titled "Influenza Vaccine Response during the Start of a Pandemic". In previous work, we have shown that HEK-293 cell culture in suspension and serum free medium is an efficient production platform for cell culture manufacturing of influenza candidate vaccines. This report, took advantage of, recombinant DNA technology using Reverse Genetics of influenza strains, and advances in the large-scale transfection of suspension cultured HEK-293 cells. We demonstrate the efficient generation of H1N1 with the PR8 backbone reassortant under controlled bioreactor conditions in two sequential steps (transfection/rescue and infection/production). This approach could deliver a CVV for influenza vaccine manufacturing within two-weeks, starting from HA and NA pandemic sequences. Furthermore, the scalability of the transfection technology combined with the HEK-293 platform has been extensively demonstrated at \textgreater100L scale for several biologics, including recombinant viruses. Thus, this innovative approach is better suited to rationally engineer and mass produce influenza CVV within significantly shorter timelines to enable an effective global response in pandemic situations.</p>
</abstract>
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