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

Identifieur interne : 001C69 ( Ncbi/Merge ); précédent : 001C68; suivant : 001C70

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 : pubmed:28495315

Descripteurs français

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 >100L 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.

DOI: 10.1016/j.vaccine.2017.04.065
PubMed: 28495315

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Le document en format XML

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<div type="abstract" xml:lang="en">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 >100L 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.</div>
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<ForeName>Rafael</ForeName>
<Initials>R</Initials>
<AffiliationInfo>
<Affiliation>Department of Bioengineering, McGill University, Montréal, Québec, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Venereo-Sanchez</LastName>
<ForeName>Alina</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Vaccine Program, Human Health Therapeutics, National Research Council, Montréal, Québec, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Montes</LastName>
<ForeName>Johnny</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Vaccine Program, Human Health Therapeutics, National Research Council, Montréal, Québec, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Manceur</LastName>
<ForeName>Aziza P</ForeName>
<Initials>AP</Initials>
<AffiliationInfo>
<Affiliation>Vaccine Program, Human Health Therapeutics, National Research Council, Montréal, Québec, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Ansorge</LastName>
<ForeName>Sven</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Vaccine Program, Human Health Therapeutics, National Research Council, Montréal, Québec, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Petiot</LastName>
<ForeName>Emma</ForeName>
<Initials>E</Initials>
<AffiliationInfo>
<Affiliation>Virologie et Pathologie Humaine - VirPath Team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Rosa-Calatrava</LastName>
<ForeName>Manuel</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Virologie et Pathologie Humaine - VirPath Team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kamen</LastName>
<ForeName>Amine</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Department of Bioengineering, McGill University, Montréal, Québec, Canada; Vaccine Program, Human Health Therapeutics, National Research Council, Montréal, Québec, Canada. Electronic address: amine.kamen@mcgill.ca.</Affiliation>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<Year>2017</Year>
<Month>05</Month>
<Day>08</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>Netherlands</Country>
<MedlineTA>Vaccine</MedlineTA>
<NlmUniqueID>8406899</NlmUniqueID>
<ISSNLinking>0264-410X</ISSNLinking>
</MedlineJournalInfo>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007252">Influenza Vaccines</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
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</MeshHeading>
<MeshHeading>
<DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName>
<QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006385" MajorTopicYN="N">Hemagglutination Inhibition Tests</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D053118" MajorTopicYN="N">Influenza A Virus, H1N1 Subtype</DescriptorName>
<QualifierName UI="Q000254" MajorTopicYN="Y">growth & development</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007252" MajorTopicYN="N">Influenza Vaccines</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016865" MajorTopicYN="N">Reassortant Viruses</DescriptorName>
<QualifierName UI="Q000254" MajorTopicYN="N">growth & development</QualifierName>
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<DescriptorName UI="D059386" MajorTopicYN="Y">Reverse Genetics</DescriptorName>
</MeshHeading>
<MeshHeading>
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</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014776" MajorTopicYN="Y">Virus Cultivation</DescriptorName>
</MeshHeading>
</MeshHeadingList>
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<Keyword MajorTopicYN="Y">Candidate Vaccine Virus (CVV)</Keyword>
<Keyword MajorTopicYN="Y">Influenza virus</Keyword>
<Keyword MajorTopicYN="Y">Large-scale</Keyword>
<Keyword MajorTopicYN="Y">Pandemic</Keyword>
<Keyword MajorTopicYN="Y">Reverse genetics</Keyword>
<Keyword MajorTopicYN="Y">Suspension cell culture</Keyword>
<Keyword MajorTopicYN="Y">Transient transfection</Keyword>
<Keyword MajorTopicYN="Y">Vaccines</Keyword>
</KeywordList>
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<Month>01</Month>
<Day>29</Day>
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<PubMedPubDate PubStatus="revised">
<Year>2017</Year>
<Month>04</Month>
<Day>14</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2017</Year>
<Month>04</Month>
<Day>23</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2017</Year>
<Month>5</Month>
<Day>13</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2017</Year>
<Month>12</Month>
<Day>8</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2017</Year>
<Month>5</Month>
<Day>13</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">28495315</ArticleId>
<ArticleId IdType="pii">S0264-410X(17)30557-1</ArticleId>
<ArticleId IdType="doi">10.1016/j.vaccine.2017.04.065</ArticleId>
</ArticleIdList>
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<affiliations>
<list>
<country>
<li>Canada</li>
<li>France</li>
</country>
<region>
<li>Auvergne-Rhône-Alpes</li>
<li>Québec</li>
<li>Rhône-Alpes</li>
</region>
<settlement>
<li>Lyon</li>
<li>Montréal</li>
</settlement>
<orgName>
<li>Université Claude Bernard Lyon 1</li>
<li>Université McGill</li>
</orgName>
</list>
<tree>
<country name="Canada">
<region name="Québec">
<name sortKey="Milian, Ernest" sort="Milian, Ernest" uniqKey="Milian E" first="Ernest" last="Milián">Ernest Milián</name>
</region>
<name sortKey="Ansorge, Sven" sort="Ansorge, Sven" uniqKey="Ansorge S" first="Sven" last="Ansorge">Sven Ansorge</name>
<name sortKey="Biaggio, Rafael" sort="Biaggio, Rafael" uniqKey="Biaggio R" first="Rafael" last="Biaggio">Rafael Biaggio</name>
<name sortKey="Kamen, Amine" sort="Kamen, Amine" uniqKey="Kamen A" first="Amine" last="Kamen">Amine Kamen</name>
<name sortKey="Manceur, Aziza P" sort="Manceur, Aziza P" uniqKey="Manceur A" first="Aziza P" last="Manceur">Aziza P. Manceur</name>
<name sortKey="Montes, Johnny" sort="Montes, Johnny" uniqKey="Montes J" first="Johnny" last="Montes">Johnny Montes</name>
<name sortKey="Venereo Sanchez, Alina" sort="Venereo Sanchez, Alina" uniqKey="Venereo Sanchez A" first="Alina" last="Venereo-Sanchez">Alina Venereo-Sanchez</name>
</country>
<country name="France">
<region name="Auvergne-Rhône-Alpes">
<name sortKey="Julien, Thomas" sort="Julien, Thomas" uniqKey="Julien T" first="Thomas" last="Julien">Thomas Julien</name>
</region>
<name sortKey="Petiot, Emma" sort="Petiot, Emma" uniqKey="Petiot E" first="Emma" last="Petiot">Emma Petiot</name>
<name sortKey="Rosa Calatrava, Manuel" sort="Rosa Calatrava, Manuel" uniqKey="Rosa Calatrava M" first="Manuel" last="Rosa-Calatrava">Manuel Rosa-Calatrava</name>
</country>
</tree>
</affiliations>
</record>

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