MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation
Identifieur interne : 001732 ( Istex/Corpus ); précédent : 001731; suivant : 001733MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation
Auteurs : Yvonne Genzel ; Christian Dietzsch ; Erdmann Rapp ; Jana Schwarzer ; Udo ReichlSource :
- Applied Microbiology and Biotechnology [ 0175-7598 ] ; 2010-09-01.
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Abstract
Abstract: Over the last decade, adherent MDCK (Madin Darby canine kidney) and Vero cells have attracted considerable attention for production of cell culture-derived influenza vaccines. While numerous publications deal with the design and the optimization of corresponding upstream processes, one-to-one comparisons of these cell lines under comparable cultivation conditions have largely been neglected. Therefore, a direct comparison of influenza virus production with adherent MDCK and Vero cells in T-flasks, roller bottles, and lab-scale bioreactors was performed in this study. First, virus seeds had to be adapted to Vero cells by multiple passages. Glycan analysis of the hemagglutinin (HA) protein showed that for influenza A/PR/8/34 H1N1, three passages were sufficient to achieve a stable new N-glycan fingerprint, higher yields, and a faster increase to maximum HA titers. Compared to MDCK cells, virus production in serum-free medium with Vero cells was highly sensitive to trypsin concentration. Virus stability at 37 °C for different virus strains showed differences depending on medium, virus strain, and cell line. After careful adjustment of corresponding parameters, comparable productivity was obtained with both host cell lines in small-scale cultivation systems. However, using these cultivation conditions in lab-scale bioreactors (stirred tank, wave bioreactor) resulted in lower productivities for Vero cells.
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DOI: 10.1007/s00253-010-2742-9
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Y" first="Yvonne" last="Genzel">Yvonne Genzel</name><affiliation><mods:affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: genzel@mpi-magdeburg.mpg.de</mods:affiliation></affiliation></author><author><name sortKey="Dietzsch, Christian" sort="Dietzsch, Christian" uniqKey="Dietzsch C" first="Christian" last="Dietzsch">Christian Dietzsch</name><affiliation><mods:affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Lehrstuhl für Bioverfahrenstechnik, Dresden University of Technology, Bergstr. 120, 01069, Dresden, Germany</mods:affiliation></affiliation></author><author><name sortKey="Rapp, Erdmann" sort="Rapp, Erdmann" uniqKey="Rapp E" first="Erdmann" last="Rapp">Erdmann Rapp</name><affiliation><mods:affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schwarzer, Jana" sort="Schwarzer, Jana" uniqKey="Schwarzer J" first="Jana" last="Schwarzer">Jana Schwarzer</name><affiliation><mods:affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Reichl, Udo" sort="Reichl, Udo" uniqKey="Reichl U" first="Udo" last="Reichl">Udo Reichl</name><affiliation><mods:affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Lehrstuhl für Bioprozesstechnik, Otto-von-Guericke-Universität Magdeburg, Universitätsplatz 2, 39106, Magdeburg, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Applied Microbiology and Biotechnology</title><title level="j" type="abbrev">Appl Microbiol Biotechnol</title><idno type="ISSN">0175-7598</idno><idno type="eISSN">1432-0614</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2010-09-01">2010-09-01</date><biblScope unit="volume">88</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="461">461</biblScope><biblScope unit="page" to="475">475</biblScope></imprint><idno type="ISSN">0175-7598</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0175-7598</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Bioreactor</term><term>Glycosylation</term><term>Influenza virus</term><term>TCID50 stability</term><term>Trypsin</term><term>Vaccine production</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Over the last decade, adherent MDCK (Madin Darby canine kidney) and Vero cells have attracted considerable attention for production of cell culture-derived influenza vaccines. While numerous publications deal with the design and the optimization of corresponding upstream processes, one-to-one comparisons of these cell lines under comparable cultivation conditions have largely been neglected. Therefore, a direct comparison of influenza virus production with adherent MDCK and Vero cells in T-flasks, roller bottles, and lab-scale bioreactors was performed in this study. First, virus seeds had to be adapted to Vero cells by multiple passages. Glycan analysis of the hemagglutinin (HA) protein showed that for influenza A/PR/8/34 H1N1, three passages were sufficient to achieve a stable new N-glycan fingerprint, higher yields, and a faster increase to maximum HA titers. Compared to MDCK cells, virus production in serum-free medium with Vero cells was highly sensitive to trypsin concentration. Virus stability at 37 °C for different virus strains showed differences depending on medium, virus strain, and cell line. After careful adjustment of corresponding parameters, comparable productivity was obtained with both host cell lines in small-scale cultivation systems. However, using these cultivation conditions in lab-scale bioreactors (stirred tank, wave bioreactor) resulted in lower productivities for Vero cells.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Yvonne Genzel</name><affiliations><json:string>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</json:string><json:string>E-mail: genzel@mpi-magdeburg.mpg.de</json:string></affiliations></json:item><json:item><name>Christian Dietzsch</name><affiliations><json:string>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</json:string><json:string>Lehrstuhl für Bioverfahrenstechnik, Dresden University of Technology, Bergstr. 120, 01069, Dresden, Germany</json:string></affiliations></json:item><json:item><name>Erdmann Rapp</name><affiliations><json:string>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</json:string></affiliations></json:item><json:item><name>Jana Schwarzer</name><affiliations><json:string>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</json:string></affiliations></json:item><json:item><name>Udo Reichl</name><affiliations><json:string>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</json:string><json:string>Lehrstuhl für Bioprozesstechnik, Otto-von-Guericke-Universität Magdeburg, Universitätsplatz 2, 39106, Magdeburg, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Influenza virus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Vaccine production</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TCID50 stability</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Trypsin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Glycosylation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Bioreactor</value></json:item></subject><articleId><json:string>2742</json:string><json:string>s00253-010-2742-9</json:string></articleId><arkIstex>ark:/67375/VQC-BDCGX7J9-T</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: Over the last decade, adherent MDCK (Madin Darby canine kidney) and Vero cells have attracted considerable attention for production of cell culture-derived influenza vaccines. While numerous publications deal with the design and the optimization of corresponding upstream processes, one-to-one comparisons of these cell lines under comparable cultivation conditions have largely been neglected. Therefore, a direct comparison of influenza virus production with adherent MDCK and Vero cells in T-flasks, roller bottles, and lab-scale bioreactors was performed in this study. First, virus seeds had to be adapted to Vero cells by multiple passages. Glycan analysis of the hemagglutinin (HA) protein showed that for influenza A/PR/8/34 H1N1, three passages were sufficient to achieve a stable new N-glycan fingerprint, higher yields, and a faster increase to maximum HA titers. Compared to MDCK cells, virus production in serum-free medium with Vero cells was highly sensitive to trypsin concentration. Virus stability at 37 °C for different virus strains showed differences depending on medium, virus strain, and cell line. After careful adjustment of corresponding parameters, comparable productivity was obtained with both host cell lines in small-scale cultivation systems. However, using these cultivation conditions in lab-scale bioreactors (stirred tank, wave bioreactor) resulted in lower productivities for Vero cells.</abstract><qualityIndicators><score>9.4</score><pdfWordCount>9212</pdfWordCount><pdfCharCount>58453</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>15</pdfPageCount><pdfPageSize>595.276 x 790.866 pts</pdfPageSize><refBibsNative>false</refBibsNative><abstractWordCount>200</abstractWordCount><abstractCharCount>1434</abstractCharCount><keywordCount>6</keywordCount></qualityIndicators><title>MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation</title><genre><json:string>research-article</json:string></genre><host><title>Applied Microbiology and 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While numerous publications deal with the design and the optimization of corresponding upstream processes, one-to-one comparisons of these cell lines under comparable cultivation conditions have largely been neglected. Therefore, a direct comparison of influenza virus production with adherent MDCK and Vero cells in T-flasks, roller bottles, and lab-scale bioreactors was performed in this study. First, virus seeds had to be adapted to Vero cells by multiple passages. Glycan analysis of the hemagglutinin (HA) protein showed that for influenza A/PR/8/34 H1N1, three passages were sufficient to achieve a stable new N-glycan fingerprint, higher yields, and a faster increase to maximum HA titers. Compared to MDCK cells, virus production in serum-free medium with Vero cells was highly sensitive to trypsin concentration. Virus stability at 37 °C for different virus strains showed differences depending on medium, virus strain, and cell line. After careful adjustment of corresponding parameters, comparable productivity was obtained with both host cell lines in small-scale cultivation systems. However, using these cultivation conditions in lab-scale bioreactors (stirred tank, wave bioreactor) resulted in lower productivities for Vero cells.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Influenza virus</term></item><item><term>Vaccine production</term></item><item><term>TCID50 stability</term></item><item><term>Trypsin</term></item><item><term>Glycosylation</term></item><item><term>Bioreactor</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Chemistry</head><item><term>Microbial Genetics and Genomics</term></item><item><term>Microbiology</term></item><item><term>Biotechnology</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-04-29">Created</change><change 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Products and Process Engineering</ArticleCategory><ArticleFirstPage>461</ArticleFirstPage><ArticleLastPage>475</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2010</Year><Month>6</Month><Day>18</Day></RegistrationDate><Received><Year>2010</Year><Month>4</Month><Day>29</Day></Received><Revised><Year>2010</Year><Month>6</Month><Day>16</Day></Revised><Accepted><Year>2010</Year><Month>6</Month><Day>16</Day></Accepted><OnlineDate><Year>2010</Year><Month>7</Month><Day>9</Day></OnlineDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Springer-Verlag</CopyrightHolderName><CopyrightYear>2010</CopyrightYear></ArticleCopyright><ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant><AbstractGrant Grant="OpenAccess"></AbstractGrant><BodyPDFGrant Grant="Restricted"></BodyPDFGrant><BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant><BibliographyGrant Grant="Restricted"></BibliographyGrant><ESMGrant Grant="Restricted"></ESMGrant></ArticleGrants></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1" CorrespondingAffiliationID="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Yvonne</GivenName><FamilyName>Genzel</FamilyName></AuthorName><Contact><Phone>+49-391-6110257</Phone><Fax>+49-391-6110203</Fax><Email>genzel@mpi-magdeburg.mpg.de</Email></Contact></Author><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Christian</GivenName><FamilyName>Dietzsch</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Erdmann</GivenName><FamilyName>Rapp</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Jana</GivenName><FamilyName>Schwarzer</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff3"><AuthorName DisplayOrder="Western"><GivenName>Udo</GivenName><FamilyName>Reichl</FamilyName></AuthorName></Author><Affiliation ID="Aff1"><OrgName>Max Planck Institute for Dynamics of Complex Technical Systems</OrgName><OrgAddress><Street>Sandtorstr. 1</Street><Postcode>39106</Postcode><City>Magdeburg</City><Country Code="DE">Germany</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgDivision>Lehrstuhl für Bioverfahrenstechnik</OrgDivision><OrgName>Dresden University of Technology</OrgName><OrgAddress><Street>Bergstr. 120</Street><Postcode>01069</Postcode><City>Dresden</City><Country Code="DE">Germany</Country></OrgAddress></Affiliation><Affiliation ID="Aff3"><OrgDivision>Lehrstuhl für Bioprozesstechnik</OrgDivision><OrgName>Otto-von-Guericke-Universität Magdeburg</OrgName><OrgAddress><Street>Universitätsplatz 2</Street><Postcode>39106</Postcode><City>Magdeburg</City><Country Code="DE">Germany</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En" OutputMedium="All"><Heading>Abstract</Heading><Para>Over the last decade, adherent MDCK (Madin Darby canine kidney) and Vero cells have attracted considerable attention for production of cell culture-derived influenza vaccines. While numerous publications deal with the design and the optimization of corresponding upstream processes, one-to-one comparisons of these cell lines under comparable cultivation conditions have largely been neglected. Therefore, a direct comparison of influenza virus production with adherent MDCK and Vero cells in T-flasks, roller bottles, and lab-scale bioreactors was performed in this study. First, virus seeds had to be adapted to Vero cells by multiple passages. Glycan analysis of the hemagglutinin (HA) protein showed that for influenza A/PR/8/34 H1N1, three passages were sufficient to achieve a stable new <Emphasis Type="Italic">N-</Emphasis>glycan fingerprint, higher yields, and a faster increase to maximum HA titers. Compared to MDCK cells, virus production in serum-free medium with Vero cells was highly sensitive to trypsin concentration. Virus stability at 37 °C for different virus strains showed differences depending on medium, virus strain, and cell line. After careful adjustment of corresponding parameters, comparable productivity was obtained with both host cell lines in small-scale cultivation systems. However, using these cultivation conditions in lab-scale bioreactors (stirred tank, wave bioreactor) resulted in lower productivities for Vero cells.</Para></Abstract><KeywordGroup Language="En" OutputMedium="All"><Heading>Keywords</Heading><Keyword>Influenza virus</Keyword><Keyword>Vaccine production</Keyword><Keyword>TCID<Subscript>50</Subscript> stability</Keyword><Keyword>Trypsin</Keyword><Keyword>Glycosylation</Keyword><Keyword>Bioreactor</Keyword></KeywordGroup></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Yvonne</namePart><namePart type="family">Genzel</namePart><affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</affiliation><affiliation>E-mail: genzel@mpi-magdeburg.mpg.de</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christian</namePart><namePart type="family">Dietzsch</namePart><affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</affiliation><affiliation>Lehrstuhl für Bioverfahrenstechnik, Dresden University of Technology, Bergstr. 120, 01069, Dresden, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Erdmann</namePart><namePart type="family">Rapp</namePart><affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jana</namePart><namePart type="family">Schwarzer</namePart><affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Udo</namePart><namePart type="family">Reichl</namePart><affiliation>Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106, Magdeburg, Germany</affiliation><affiliation>Lehrstuhl für Bioprozesstechnik, Otto-von-Guericke-Universität Magdeburg, Universitätsplatz 2, 39106, Magdeburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Springer-Verlag</publisher><place><placeTerm type="text">Berlin/Heidelberg</placeTerm></place><dateCreated encoding="w3cdtf">2010-04-29</dateCreated><dateIssued encoding="w3cdtf">2010-09-01</dateIssued><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: Over the last decade, adherent MDCK (Madin Darby canine kidney) and Vero cells have attracted considerable attention for production of cell culture-derived influenza vaccines. While numerous publications deal with the design and the optimization of corresponding upstream processes, one-to-one comparisons of these cell lines under comparable cultivation conditions have largely been neglected. Therefore, a direct comparison of influenza virus production with adherent MDCK and Vero cells in T-flasks, roller bottles, and lab-scale bioreactors was performed in this study. First, virus seeds had to be adapted to Vero cells by multiple passages. Glycan analysis of the hemagglutinin (HA) protein showed that for influenza A/PR/8/34 H1N1, three passages were sufficient to achieve a stable new N-glycan fingerprint, higher yields, and a faster increase to maximum HA titers. Compared to MDCK cells, virus production in serum-free medium with Vero cells was highly sensitive to trypsin concentration. Virus stability at 37 °C for different virus strains showed differences depending on medium, virus strain, and cell line. After careful adjustment of corresponding parameters, comparable productivity was obtained with both host cell lines in small-scale cultivation systems. However, using these cultivation conditions in lab-scale bioreactors (stirred tank, wave bioreactor) resulted in lower productivities for Vero cells.</abstract><note>Biotechnological Products and Process Engineering</note><subject lang="en"><genre>Keywords</genre><topic>Influenza virus</topic><topic>Vaccine production</topic><topic>TCID50 stability</topic><topic>Trypsin</topic><topic>Glycosylation</topic><topic>Bioreactor</topic></subject><relatedItem type="host"><titleInfo><title>Applied Microbiology and Biotechnology</title></titleInfo><titleInfo type="abbreviated"><title>Appl Microbiol Biotechnol</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>Springer</publisher><dateIssued encoding="w3cdtf">2010-08-21</dateIssued><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><subject><genre>Chemistry</genre><topic>Microbial Genetics and Genomics</topic><topic>Microbiology</topic><topic>Biotechnology</topic></subject><identifier type="ISSN">0175-7598</identifier><identifier type="eISSN">1432-0614</identifier><identifier type="JournalID">253</identifier><identifier type="IssueArticleCount">18</identifier><identifier type="VolumeIssueCount">6</identifier><part><date>2010</date><detail type="volume"><number>88</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="pages"><start>461</start><end>475</end></extent></part><recordInfo><recordOrigin>Springer-Verlag, 2010</recordOrigin></recordInfo></relatedItem><identifier type="istex">BBABAE97F5BD0E07F6ED72D3F167D72CDAA31759</identifier><identifier type="ark">ark:/67375/VQC-BDCGX7J9-T</identifier><identifier type="DOI">10.1007/s00253-010-2742-9</identifier><identifier type="ArticleID">2742</identifier><identifier type="ArticleID">s00253-010-2742-9</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer-Verlag, 2010</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Springer-Verlag, 2010</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-BDCGX7J9-T/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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