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Inducible expression of antigens in plants: a study focused on peptides related to multiple sclerosis immunotherapy.

Identifieur interne : 000131 ( Main/Exploration ); précédent : 000130; suivant : 000132

Inducible expression of antigens in plants: a study focused on peptides related to multiple sclerosis immunotherapy.

Auteurs : Jaime I. Arevalo-Villalobos [Mexique] ; Dania O. Govea-Alonso [Mexique] ; Bernardo Ba Uelos-Hernández [Mexique] ; Omar González-Ortega [Mexique] ; Sergio Zarazúa [Mexique] ; Sergio Rosales-Mendoza [Mexique]

Source :

RBID : pubmed:32387449

Descripteurs français

English descriptors

Abstract

Multiple sclerosis (MS) affects 2.3 million patients worldwide with no effective treatments available thus far. Depletion of autoreactive T-cells is considered the basis for immunotherapeutic approaches. For this purpose the peptides BV5S2, BV6S5, and BV13S1 have been identified as candidates for the development of a MS vaccine. Herein, the plant-based simultaneous production of these peptides is described as an effort to generate a new model of MS immunotherapy. A polyprotein comprising the sequence of the target peptides was designed having the picornaviral 2A sequence in between to mediate the release of the individual peptides upon translation. A codon optimized gene was cloned in vectors mediating constitutive (CaMV35S promoter) or inducible (AlcA promoter) expression. No transgenic tobacco plants were recovered from the constitutive vector suggesting toxicity of the target peptides. In contrast, several transformed lines were obtained with the inducible vector. The individual BV5S2, BV6S5, and BV13S1 peptides were detected in transformed lines upon ethanol-mediated induction and a quantitative analysis based on a OVA conjugate carrying the three peptides revealed accumulation levels up to 0.5 μg g-1 FW leaves. The plant-made peptides were able to induce humoral responses in orally immunized mice. This platform will be useful in the development of alternative immunotherapies against MS having low cost and safety as main attributes. Moreover the platform represents an attractive alternative for the expression of antigens having detrimental effects in plants.

DOI: 10.1016/j.jbiotec.2020.03.013
PubMed: 32387449


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<term>Animals (MeSH)</term>
<term>Cysteine Endopeptidases (genetics)</term>
<term>Gene Expression (MeSH)</term>
<term>Genetic Vectors (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Immunization (MeSH)</term>
<term>Immunotherapy (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Multiple Sclerosis (immunology)</term>
<term>Multiple Sclerosis (therapy)</term>
<term>Peptide Fragments (genetics)</term>
<term>Peptide Fragments (immunology)</term>
<term>Plants, Genetically Modified (genetics)</term>
<term>Plants, Genetically Modified (metabolism)</term>
<term>Promoter Regions, Genetic (genetics)</term>
<term>Receptors, Antigen, T-Cell (genetics)</term>
<term>Receptors, Antigen, T-Cell (immunology)</term>
<term>Tobacco (genetics)</term>
<term>Tobacco (metabolism)</term>
<term>Vaccines, Subunit (genetics)</term>
<term>Vaccines, Subunit (immunology)</term>
<term>Viral Proteins (genetics)</term>
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<term>Animaux (MeSH)</term>
<term>Cysteine endopeptidases (génétique)</term>
<term>Expression des gènes (MeSH)</term>
<term>Fragments peptidiques (génétique)</term>
<term>Fragments peptidiques (immunologie)</term>
<term>Humains (MeSH)</term>
<term>Immunisation (MeSH)</term>
<term>Immunothérapie (MeSH)</term>
<term>Protéines virales (génétique)</term>
<term>Récepteurs aux antigènes des cellules T (génétique)</term>
<term>Récepteurs aux antigènes des cellules T (immunologie)</term>
<term>Régions promotrices (génétique) (génétique)</term>
<term>Sclérose en plaques (immunologie)</term>
<term>Sclérose en plaques (thérapie)</term>
<term>Souris (MeSH)</term>
<term>Tabac (génétique)</term>
<term>Tabac (métabolisme)</term>
<term>Vaccins sous-unitaires (génétique)</term>
<term>Vaccins sous-unitaires (immunologie)</term>
<term>Vecteurs génétiques (MeSH)</term>
<term>Végétaux génétiquement modifiés (génétique)</term>
<term>Végétaux génétiquement modifiés (métabolisme)</term>
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<term>Peptide Fragments</term>
<term>Receptors, Antigen, T-Cell</term>
<term>Vaccines, Subunit</term>
<term>Viral Proteins</term>
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<term>Plants, Genetically Modified</term>
<term>Promoter Regions, Genetic</term>
<term>Tobacco</term>
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<term>Cysteine endopeptidases</term>
<term>Fragments peptidiques</term>
<term>Protéines virales</term>
<term>Récepteurs aux antigènes des cellules T</term>
<term>Régions promotrices (génétique)</term>
<term>Tabac</term>
<term>Vaccins sous-unitaires</term>
<term>Végétaux génétiquement modifiés</term>
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<term>Fragments peptidiques</term>
<term>Récepteurs aux antigènes des cellules T</term>
<term>Sclérose en plaques</term>
<term>Vaccins sous-unitaires</term>
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<term>Multiple Sclerosis</term>
<term>Peptide Fragments</term>
<term>Receptors, Antigen, T-Cell</term>
<term>Vaccines, Subunit</term>
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<term>Plants, Genetically Modified</term>
<term>Tobacco</term>
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<term>Végétaux génétiquement modifiés</term>
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<term>Gene Expression</term>
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<term>Expression des gènes</term>
<term>Humains</term>
<term>Immunisation</term>
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<div type="abstract" xml:lang="en">Multiple sclerosis (MS) affects 2.3 million patients worldwide with no effective treatments available thus far. Depletion of autoreactive T-cells is considered the basis for immunotherapeutic approaches. For this purpose the peptides BV5S2, BV6S5, and BV13S1 have been identified as candidates for the development of a MS vaccine. Herein, the plant-based simultaneous production of these peptides is described as an effort to generate a new model of MS immunotherapy. A polyprotein comprising the sequence of the target peptides was designed having the picornaviral 2A sequence in between to mediate the release of the individual peptides upon translation. A codon optimized gene was cloned in vectors mediating constitutive (CaMV35S promoter) or inducible (AlcA promoter) expression. No transgenic tobacco plants were recovered from the constitutive vector suggesting toxicity of the target peptides. In contrast, several transformed lines were obtained with the inducible vector. The individual BV5S2, BV6S5, and BV13S1 peptides were detected in transformed lines upon ethanol-mediated induction and a quantitative analysis based on a OVA conjugate carrying the three peptides revealed accumulation levels up to 0.5 μg g
<sup>-1</sup>
FW leaves. The plant-made peptides were able to induce humoral responses in orally immunized mice. This platform will be useful in the development of alternative immunotherapies against MS having low cost and safety as main attributes. Moreover the platform represents an attractive alternative for the expression of antigens having detrimental effects in plants.</div>
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<AbstractText>Multiple sclerosis (MS) affects 2.3 million patients worldwide with no effective treatments available thus far. Depletion of autoreactive T-cells is considered the basis for immunotherapeutic approaches. For this purpose the peptides BV5S2, BV6S5, and BV13S1 have been identified as candidates for the development of a MS vaccine. Herein, the plant-based simultaneous production of these peptides is described as an effort to generate a new model of MS immunotherapy. A polyprotein comprising the sequence of the target peptides was designed having the picornaviral 2A sequence in between to mediate the release of the individual peptides upon translation. A codon optimized gene was cloned in vectors mediating constitutive (CaMV35S promoter) or inducible (AlcA promoter) expression. No transgenic tobacco plants were recovered from the constitutive vector suggesting toxicity of the target peptides. In contrast, several transformed lines were obtained with the inducible vector. The individual BV5S2, BV6S5, and BV13S1 peptides were detected in transformed lines upon ethanol-mediated induction and a quantitative analysis based on a OVA conjugate carrying the three peptides revealed accumulation levels up to 0.5 μg g
<sup>-1</sup>
FW leaves. The plant-made peptides were able to induce humoral responses in orally immunized mice. This platform will be useful in the development of alternative immunotherapies against MS having low cost and safety as main attributes. Moreover the platform represents an attractive alternative for the expression of antigens having detrimental effects in plants.</AbstractText>
<CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation>
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<LastName>Arevalo-Villalobos</LastName>
<ForeName>Jaime I</ForeName>
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<Affiliation>Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, San Luis Potosí, 78210, Mexico; Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona 550, Lomas 2ª Sección, San Luis Potosí, 78210, Mexico.</Affiliation>
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<ForeName>Dania O</ForeName>
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<Affiliation>Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, San Luis Potosí, 78210, Mexico; Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona 550, Lomas 2ª Sección, San Luis Potosí, 78210, Mexico.</Affiliation>
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<Author ValidYN="Y">
<LastName>González-Ortega</LastName>
<ForeName>Omar</ForeName>
<Initials>O</Initials>
<AffiliationInfo>
<Affiliation>Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, San Luis Potosí, 78210, Mexico.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zarazúa</LastName>
<ForeName>Sergio</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, San Luis Potosí, 78210, Mexico.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Rosales-Mendoza</LastName>
<ForeName>Sergio</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, San Luis Potosí, 78210, Mexico; Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona 550, Lomas 2ª Sección, San Luis Potosí, 78210, Mexico. Electronic address: rosales.s@uaslp.mx.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2020</Year>
<Month>05</Month>
<Day>06</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>Netherlands</Country>
<MedlineTA>J Biotechnol</MedlineTA>
<NlmUniqueID>8411927</NlmUniqueID>
<ISSNLinking>0168-1656</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D010446">Peptide Fragments</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011948">Receptors, Antigen, T-Cell</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D022223">Vaccines, Subunit</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 3.4.22.-</RegistryNumber>
<NameOfSubstance UI="D003546">Cysteine Endopeptidases</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 3.4.22.29</RegistryNumber>
<NameOfSubstance UI="C057400">picornain 2A, Picornavirus</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D003546" MajorTopicYN="N">Cysteine Endopeptidases</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005822" MajorTopicYN="N">Genetic Vectors</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007114" MajorTopicYN="N">Immunization</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007167" MajorTopicYN="Y">Immunotherapy</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009103" MajorTopicYN="N">Multiple Sclerosis</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010446" MajorTopicYN="N">Peptide Fragments</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D030821" MajorTopicYN="N">Plants, Genetically Modified</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011401" MajorTopicYN="N">Promoter Regions, Genetic</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011948" MajorTopicYN="N">Receptors, Antigen, T-Cell</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014026" MajorTopicYN="N">Tobacco</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D022223" MajorTopicYN="N">Vaccines, Subunit</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">2A peptide</Keyword>
<Keyword MajorTopicYN="N">Algevir</Keyword>
<Keyword MajorTopicYN="N">T cell receptor peptide</Keyword>
<Keyword MajorTopicYN="N">multicomponent vaccine</Keyword>
<Keyword MajorTopicYN="N">multiple sclerosis immunotherapy</Keyword>
<Keyword MajorTopicYN="N">plant-made vaccine</Keyword>
</KeywordList>
<CoiStatement>Declaration of Competing Interest The authors declare no conflict of interests.</CoiStatement>
</MedlineCitation>
<PubmedData>
<History>
<PubMedPubDate PubStatus="received">
<Year>2020</Year>
<Month>01</Month>
<Day>27</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised">
<Year>2020</Year>
<Month>03</Month>
<Day>26</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2020</Year>
<Month>03</Month>
<Day>27</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2020</Year>
<Month>5</Month>
<Day>11</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2020</Year>
<Month>11</Month>
<Day>18</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2020</Year>
<Month>5</Month>
<Day>11</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">32387449</ArticleId>
<ArticleId IdType="pii">S0168-1656(20)30076-6</ArticleId>
<ArticleId IdType="doi">10.1016/j.jbiotec.2020.03.013</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations>
<list>
<country>
<li>Mexique</li>
</country>
</list>
<tree>
<country name="Mexique">
<noRegion>
<name sortKey="Arevalo Villalobos, Jaime I" sort="Arevalo Villalobos, Jaime I" uniqKey="Arevalo Villalobos J" first="Jaime I" last="Arevalo-Villalobos">Jaime I. Arevalo-Villalobos</name>
</noRegion>
<name sortKey="Ba Uelos Hernandez, Bernardo" sort="Ba Uelos Hernandez, Bernardo" uniqKey="Ba Uelos Hernandez B" first="Bernardo" last="Ba Uelos-Hernández">Bernardo Ba Uelos-Hernández</name>
<name sortKey="Gonzalez Ortega, Omar" sort="Gonzalez Ortega, Omar" uniqKey="Gonzalez Ortega O" first="Omar" last="González-Ortega">Omar González-Ortega</name>
<name sortKey="Govea Alonso, Dania O" sort="Govea Alonso, Dania O" uniqKey="Govea Alonso D" first="Dania O" last="Govea-Alonso">Dania O. Govea-Alonso</name>
<name sortKey="Rosales Mendoza, Sergio" sort="Rosales Mendoza, Sergio" uniqKey="Rosales Mendoza S" first="Sergio" last="Rosales-Mendoza">Sergio Rosales-Mendoza</name>
<name sortKey="Zarazua, Sergio" sort="Zarazua, Sergio" uniqKey="Zarazua S" first="Sergio" last="Zarazúa">Sergio Zarazúa</name>
</country>
</tree>
</affiliations>
</record>

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