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Biochemical composition of haemagglutinin-based influenza virus-like particle vaccine produced by transient expression in tobacco plants.

Identifieur interne : 000363 ( Main/Exploration ); précédent : 000362; suivant : 000364

Biochemical composition of haemagglutinin-based influenza virus-like particle vaccine produced by transient expression in tobacco plants.

Auteurs : François Le Mauff [France, Canada] ; Geneviève Mercier [Canada] ; Philippe Chan [France] ; Carole Burel [France] ; David Vaudry [France] ; Muriel Bardor [France] ; Louis-Philippe Vézina [Canada] ; Manon Couture [Canada] ; Patrice Lerouge [France] ; Nathalie Landry [Canada]

Source :

RBID : pubmed:25523794

Descripteurs français

English descriptors

Abstract

Influenza virus-like particles (VLPs) are noninfectious particles resembling the influenza virus representing a promising vaccine alternative to inactivated influenza virions as antigens. Medicago inc. has developed a plant-based VLP manufacturing platform allowing the large-scale production of GMP-grade influenza VLPs. In this article, we report on the biochemical compositions of these plant-based influenza candidate vaccines, more particularly the characterization of the N-glycan profiles of the viral haemagglutinins H1 and H5 proteins as well as the tobacco-derived lipid content and residual impurities. Mass spectrometry analyses showed that all N-glycosylation sites of the extracellular domain of the recombinant haemagglutinins carry plant-specific complex-type N-glycans having core α(1,3)-fucose, core β(1,2)-xylose epitopes and Lewis(a) extensions. Previous phases I and II clinical studies have demonstrated that no hypersensibility nor induction of IgG or IgE directed against these glycans was observed. In addition, this article showed that the plant-made influenza vaccines are highly pure VLPs preparations while detecting no protein contaminants coming either from Agrobacterium or from the enzymes used for the enzyme-assisted extraction process. In contrast, VLPs contain few host cell proteins and glucosylceramides associated with plant lipid rafts. Identification of such raft markers, together with the type of host cell impurity identified, confirmed that the mechanism of VLP formation in planta is similar to the natural process of influenza virus assembly in mammals.

DOI: 10.1111/pbi.12301
PubMed: 25523794


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Le document en format XML

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<term>Amino Acid Sequence (MeSH)</term>
<term>Epitopes (chemistry)</term>
<term>Epitopes (immunology)</term>
<term>Gene Expression (MeSH)</term>
<term>Glycosylation (MeSH)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (chemistry)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term>
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<term>Polysaccharides (chemistry)</term>
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<term>Sphingolipids (chemistry)</term>
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<term>Données de séquences moléculaires (MeSH)</term>
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<term>Glycoprotéine hémagglutinine du virus influenza (composition chimique)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (immunologie)</term>
<term>Glycosylation (MeSH)</term>
<term>Grippe humaine (prévention et contrôle)</term>
<term>Humains (MeSH)</term>
<term>Microdomaines membranaires (MeSH)</term>
<term>Phospholipides (composition chimique)</term>
<term>Polyosides (composition chimique)</term>
<term>Protéines recombinantes (MeSH)</term>
<term>Sous-type H1N1 du virus de la grippe A (immunologie)</term>
<term>Sous-type H5N1 du virus de la grippe A (immunologie)</term>
<term>Sphingolipides (composition chimique)</term>
<term>Séquence d'acides aminés (MeSH)</term>
<term>Tabac (génétique)</term>
<term>Tabac (métabolisme)</term>
<term>Vaccins antigrippaux (immunologie)</term>
<term>Vaccins à pseudo-particules virales (immunologie)</term>
<term>Végétaux génétiquement modifiés (MeSH)</term>
<term>Épitopes (composition chimique)</term>
<term>Épitopes (immunologie)</term>
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<term>Epitopes</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Phospholipids</term>
<term>Polysaccharides</term>
<term>Sphingolipids</term>
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<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Epitopes</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Influenza Vaccines</term>
<term>Vaccines, Virus-Like Particle</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr">
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Phospholipides</term>
<term>Polyosides</term>
<term>Sphingolipides</term>
<term>Épitopes</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Tobacco</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Tabac</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
<term>Sous-type H5N1 du virus de la grippe A</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins à pseudo-particules virales</term>
<term>Épitopes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Influenza A Virus, H1N1 Subtype</term>
<term>Influenza A Virus, H5N1 Subtype</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Tobacco</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Tabac</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Influenza, Human</term>
</keywords>
<keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr">
<term>Grippe humaine</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Gene Expression</term>
<term>Glycosylation</term>
<term>Humans</term>
<term>Membrane Microdomains</term>
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<term>Recombinant Proteins</term>
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<term>Glycosylation</term>
<term>Humains</term>
<term>Microdomaines membranaires</term>
<term>Protéines recombinantes</term>
<term>Séquence d'acides aminés</term>
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<div type="abstract" xml:lang="en">Influenza virus-like particles (VLPs) are noninfectious particles resembling the influenza virus representing a promising vaccine alternative to inactivated influenza virions as antigens. Medicago inc. has developed a plant-based VLP manufacturing platform allowing the large-scale production of GMP-grade influenza VLPs. In this article, we report on the biochemical compositions of these plant-based influenza candidate vaccines, more particularly the characterization of the N-glycan profiles of the viral haemagglutinins H1 and H5 proteins as well as the tobacco-derived lipid content and residual impurities. Mass spectrometry analyses showed that all N-glycosylation sites of the extracellular domain of the recombinant haemagglutinins carry plant-specific complex-type N-glycans having core α(1,3)-fucose, core β(1,2)-xylose epitopes and Lewis(a) extensions. Previous phases I and II clinical studies have demonstrated that no hypersensibility nor induction of IgG or IgE directed against these glycans was observed. In addition, this article showed that the plant-made influenza vaccines are highly pure VLPs preparations while detecting no protein contaminants coming either from Agrobacterium or from the enzymes used for the enzyme-assisted extraction process. In contrast, VLPs contain few host cell proteins and glucosylceramides associated with plant lipid rafts. Identification of such raft markers, together with the type of host cell impurity identified, confirmed that the mechanism of VLP formation in planta is similar to the natural process of influenza virus assembly in mammals. </div>
</front>
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<ELocationID EIdType="doi" ValidYN="Y">10.1111/pbi.12301</ELocationID>
<Abstract>
<AbstractText>Influenza virus-like particles (VLPs) are noninfectious particles resembling the influenza virus representing a promising vaccine alternative to inactivated influenza virions as antigens. Medicago inc. has developed a plant-based VLP manufacturing platform allowing the large-scale production of GMP-grade influenza VLPs. In this article, we report on the biochemical compositions of these plant-based influenza candidate vaccines, more particularly the characterization of the N-glycan profiles of the viral haemagglutinins H1 and H5 proteins as well as the tobacco-derived lipid content and residual impurities. Mass spectrometry analyses showed that all N-glycosylation sites of the extracellular domain of the recombinant haemagglutinins carry plant-specific complex-type N-glycans having core α(1,3)-fucose, core β(1,2)-xylose epitopes and Lewis(a) extensions. Previous phases I and II clinical studies have demonstrated that no hypersensibility nor induction of IgG or IgE directed against these glycans was observed. In addition, this article showed that the plant-made influenza vaccines are highly pure VLPs preparations while detecting no protein contaminants coming either from Agrobacterium or from the enzymes used for the enzyme-assisted extraction process. In contrast, VLPs contain few host cell proteins and glucosylceramides associated with plant lipid rafts. Identification of such raft markers, together with the type of host cell impurity identified, confirmed that the mechanism of VLP formation in planta is similar to the natural process of influenza virus assembly in mammals. </AbstractText>
<CopyrightInformation>© 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Le Mauff</LastName>
<ForeName>François</ForeName>
<Initials>F</Initials>
<AffiliationInfo>
<Affiliation>Laboratoire Glyco-MEV EA 4358, Institut de Recherche et d'Innovation Biomédicale, Normandie Université, Mont-Saint-Aignan, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Medicago inc., Québec, QC, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Mercier</LastName>
<ForeName>Geneviève</ForeName>
<Initials>G</Initials>
<AffiliationInfo>
<Affiliation>Medicago inc., Québec, QC, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Chan</LastName>
<ForeName>Philippe</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>PISSARO Proteomic Platform, Institut de Recherche et d'Innovation Biomédicale, Normandie Université, Mont-Saint-Aignan, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Burel</LastName>
<ForeName>Carole</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Laboratoire Glyco-MEV EA 4358, Institut de Recherche et d'Innovation Biomédicale, Normandie Université, Mont-Saint-Aignan, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Vaudry</LastName>
<ForeName>David</ForeName>
<Initials>D</Initials>
<AffiliationInfo>
<Affiliation>PISSARO Proteomic Platform, Institut de Recherche et d'Innovation Biomédicale, Normandie Université, Mont-Saint-Aignan, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Bardor</LastName>
<ForeName>Muriel</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Laboratoire Glyco-MEV EA 4358, Institut de Recherche et d'Innovation Biomédicale, Normandie Université, Mont-Saint-Aignan, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Vézina</LastName>
<ForeName>Louis-Philippe</ForeName>
<Initials>LP</Initials>
<AffiliationInfo>
<Affiliation>Medicago inc., Québec, QC, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Couture</LastName>
<ForeName>Manon</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Medicago inc., Québec, QC, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lerouge</LastName>
<ForeName>Patrice</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Laboratoire Glyco-MEV EA 4358, Institut de Recherche et d'Innovation Biomédicale, Normandie Université, Mont-Saint-Aignan, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Landry</LastName>
<ForeName>Nathalie</ForeName>
<Initials>N</Initials>
<AffiliationInfo>
<Affiliation>Medicago inc., Québec, QC, Canada.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2014</Year>
<Month>12</Month>
<Day>18</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>England</Country>
<MedlineTA>Plant Biotechnol J</MedlineTA>
<NlmUniqueID>101201889</NlmUniqueID>
<ISSNLinking>1467-7644</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000939">Epitopes</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D019267">Hemagglutinin Glycoproteins, Influenza Virus</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007252">Influenza Vaccines</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D010743">Phospholipids</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011134">Polysaccharides</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011994">Recombinant Proteins</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D013107">Sphingolipids</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D058425">Vaccines, Virus-Like Particle</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000939" MajorTopicYN="N">Epitopes</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006031" MajorTopicYN="N">Glycosylation</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D019267" MajorTopicYN="N">Hemagglutinin Glycoproteins, Influenza Virus</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D053118" MajorTopicYN="N">Influenza A Virus, H1N1 Subtype</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D053124" MajorTopicYN="N">Influenza A Virus, H5N1 Subtype</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007252" MajorTopicYN="N">Influenza Vaccines</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007251" MajorTopicYN="N">Influenza, Human</DescriptorName>
<QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D021962" MajorTopicYN="N">Membrane Microdomains</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010743" MajorTopicYN="N">Phospholipids</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D030821" MajorTopicYN="N">Plants, Genetically Modified</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011134" MajorTopicYN="N">Polysaccharides</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011994" MajorTopicYN="N">Recombinant Proteins</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D013107" MajorTopicYN="N">Sphingolipids</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014026" MajorTopicYN="N">Tobacco</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D058425" MajorTopicYN="N">Vaccines, Virus-Like Particle</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">N-glycosylation</Keyword>
<Keyword MajorTopicYN="N">haemagglutinin</Keyword>
<Keyword MajorTopicYN="N">lipid raft</Keyword>
<Keyword MajorTopicYN="N">plant</Keyword>
<Keyword MajorTopicYN="N">virus-like particles</Keyword>
</KeywordList>
</MedlineCitation>
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<History>
<PubMedPubDate PubStatus="received">
<Year>2014</Year>
<Month>08</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised">
<Year>2014</Year>
<Month>10</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2014</Year>
<Month>10</Month>
<Day>26</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2014</Year>
<Month>12</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="pubmed">
<Year>2014</Year>
<Month>12</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline">
<Year>2016</Year>
<Month>2</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">25523794</ArticleId>
<ArticleId IdType="doi">10.1111/pbi.12301</ArticleId>
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<affiliations>
<list>
<country>
<li>Canada</li>
<li>France</li>
</country>
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<tree>
<country name="France">
<noRegion>
<name sortKey="Le Mauff, Francois" sort="Le Mauff, Francois" uniqKey="Le Mauff F" first="François" last="Le Mauff">François Le Mauff</name>
</noRegion>
<name sortKey="Bardor, Muriel" sort="Bardor, Muriel" uniqKey="Bardor M" first="Muriel" last="Bardor">Muriel Bardor</name>
<name sortKey="Burel, Carole" sort="Burel, Carole" uniqKey="Burel C" first="Carole" last="Burel">Carole Burel</name>
<name sortKey="Chan, Philippe" sort="Chan, Philippe" uniqKey="Chan P" first="Philippe" last="Chan">Philippe Chan</name>
<name sortKey="Lerouge, Patrice" sort="Lerouge, Patrice" uniqKey="Lerouge P" first="Patrice" last="Lerouge">Patrice Lerouge</name>
<name sortKey="Vaudry, David" sort="Vaudry, David" uniqKey="Vaudry D" first="David" last="Vaudry">David Vaudry</name>
</country>
<country name="Canada">
<noRegion>
<name sortKey="Le Mauff, Francois" sort="Le Mauff, Francois" uniqKey="Le Mauff F" first="François" last="Le Mauff">François Le Mauff</name>
</noRegion>
<name sortKey="Couture, Manon" sort="Couture, Manon" uniqKey="Couture M" first="Manon" last="Couture">Manon Couture</name>
<name sortKey="Landry, Nathalie" sort="Landry, Nathalie" uniqKey="Landry N" first="Nathalie" last="Landry">Nathalie Landry</name>
<name sortKey="Mercier, Genevieve" sort="Mercier, Genevieve" uniqKey="Mercier G" first="Geneviève" last="Mercier">Geneviève Mercier</name>
<name sortKey="Vezina, Louis Philippe" sort="Vezina, Louis Philippe" uniqKey="Vezina L" first="Louis-Philippe" last="Vézina">Louis-Philippe Vézina</name>
</country>
</tree>
</affiliations>
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