MersV1, PubMed, Checkpoint, bibRecord, 000547

Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody.

Identifieur interne : 000547 ( PubMed/Checkpoint ); précédent : 000546; suivant : 000548

Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody.

Auteurs : Sang Il Kim [Corée du Sud] ; Sujeong Kim [Corée du Sud] ; Jinhee Kim [Corée du Sud] ; So Young Chang [Corée du Sud] ; Jung Min Shim [Corée du Sud] ; Jongwha Jin [Corée du Sud] ; Chungsu Lim [Corée du Sud] ; Songyi Baek [Corée du Sud] ; Ji-Young Min [Corée du Sud] ; Wan Beom Park [Corée du Sud] ; Myoung-Don Oh [Corée du Sud] ; Seungtaek Kim [Corée du Sud] ; Junho Chung [Corée du Sud]

Source :

International journal of molecular sciences [ 1422-0067 ] ; 2019.

RBID : pubmed:31614869

Descripteurs français

KwdFr :
- Administration par inhalation, Animaux, Anticorps antiviraux (administration et posologie), Anticorps antiviraux (génétique), Anticorps antiviraux (immunologie), Anticorps neutralisants (administration et posologie), Anticorps neutralisants (génétique), Anticorps neutralisants (immunologie), Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Humains, Régions déterminant la complémentarité (génétique), Régions déterminant la complémentarité (immunologie).
MESH :
- administration et posologie : Anticorps antiviraux, Anticorps neutralisants.
- génétique : Anticorps antiviraux, Anticorps neutralisants, Régions déterminant la complémentarité.
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Régions déterminant la complémentarité.
- Administration par inhalation, Animaux, Cellules Vero, Humains.

English descriptors

KwdEn :
- Administration, Inhalation, Animals, Antibodies, Neutralizing (administration & dosage), Antibodies, Neutralizing (genetics), Antibodies, Neutralizing (immunology), Antibodies, Viral (administration & dosage), Antibodies, Viral (genetics), Antibodies, Viral (immunology), Chlorocebus aethiops, Complementarity Determining Regions (genetics), Complementarity Determining Regions (immunology), Humans, Middle East Respiratory Syndrome Coronavirus (immunology), Vero Cells.
MESH :
- chemical , administration & dosage : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , genetics : Antibodies, Neutralizing, Antibodies, Viral, Complementarity Determining Regions.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Complementarity Determining Regions.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- Administration, Inhalation, Animals, Chlorocebus aethiops, Humans, Vero Cells.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.

DOI: 10.3390/ijms20205073
PubMed: 31614869

Affiliations:

Links toward previous steps (curation, corpus...)

to stream PubMed, to step Corpus: 000395
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pubmed:31614869

Le document en format XML

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<author><name sortKey="Baek, Songyi" sort="Baek, Songyi" uniqKey="Baek S" first="Songyi" last="Baek">Songyi Baek</name>
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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31614869</PMID>
<DateCompleted><Year>2020</Year>
<Month>02</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>02</Month>
<Day>19</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1422-0067</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>20</Volume>
<Issue>20</Issue>
<PubDate><Year>2019</Year>
<Month>Oct</Month>
<Day>12</Day>
</PubDate>
</JournalIssue>
<Title>International journal of molecular sciences</Title>
<ISOAbbreviation>Int J Mol Sci</ISOAbbreviation>
</Journal>
<ArticleTitle>Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">E5073</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.3390/ijms20205073</ELocationID>
<Abstract><AbstractText>Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kim</LastName>
<ForeName>Sang Il</ForeName>
<Initials>SI</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea. sangk1128@snu.ac.kr.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea. sangk1128@snu.ac.kr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kim</LastName>
<ForeName>Sujeong</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea. sujeong5425@snu.ac.kr.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Korea. sujeong5425@snu.ac.kr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kim</LastName>
<ForeName>Jinhee</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea. jinhee.kim@ip-korea.org.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chang</LastName>
<ForeName>So Young</ForeName>
<Initials>SY</Initials>
<AffiliationInfo><Affiliation>Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea. soyoung.chang@ip-korea.org.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Shim</LastName>
<ForeName>Jung Min</ForeName>
<Initials>JM</Initials>
<AffiliationInfo><Affiliation>Zoonotic Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea. jungmin.shim@ip-korea.org.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jin</LastName>
<ForeName>Jongwha</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea. jichang011@kbiohealth.kr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lim</LastName>
<ForeName>Chungsu</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea. opern88@kbiohealth.kr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Baek</LastName>
<ForeName>Songyi</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea. bettysongyi1@kbiohealth.kr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Min</LastName>
<ForeName>Ji-Young</ForeName>
<Initials>JY</Initials>
<AffiliationInfo><Affiliation>Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea. ji-young.x.min@gsk.com.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Park</LastName>
<ForeName>Wan Beom</ForeName>
<Initials>WB</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea. wbpark1@snu.ac.kr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Oh</LastName>
<ForeName>Myoung-Don</ForeName>
<Initials>MD</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea. mdohmd@snu.ac.kr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kim</LastName>
<ForeName>Seungtaek</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Zoonotic Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea. seungtaek.kim@ip-korea.org.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chung</LastName>
<ForeName>Junho</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea. jjhchung@snu.ac.kr.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea. jjhchung@snu.ac.kr.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Korea. jjhchung@snu.ac.kr.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>NRF-2016M3A9B6918973, 2016M3A9B6918984 and 2017M3A9G6068245</GrantID>
<Agency>National Research Foundation of Korea</Agency>
<Country></Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>10</Month>
<Day>12</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Switzerland</Country>
<MedlineTA>Int J Mol Sci</MedlineTA>
<NlmUniqueID>101092791</NlmUniqueID>
<ISSNLinking>1422-0067</ISSNLinking>
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<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000280" MajorTopicYN="N">Administration, Inhalation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D022801" MajorTopicYN="N">Complementarity Determining Regions</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">MERS-CoV</Keyword>
<Keyword MajorTopicYN="N">aerosol delivery</Keyword>
<Keyword MajorTopicYN="N">antibody engineering</Keyword>
<Keyword MajorTopicYN="N">complementarity-determining regions</Keyword>
<Keyword MajorTopicYN="N">nebulizer</Keyword>
<Keyword MajorTopicYN="N">neutralizing antibody</Keyword>
<Keyword MajorTopicYN="N">pulmonary disease</Keyword>
</KeywordList>
<CoiStatement>The authors declare no conflicts of interest.</CoiStatement>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year>
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<Month>10</Month>
<Day>10</Day>
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<Month>10</Month>
<Day>10</Day>
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<Day>17</Day>
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<affiliations><list><country><li>Corée du Sud</li>
</country>
<region><li>Région capitale de Séoul</li>
</region>
<settlement><li>Séoul</li>
</settlement>
</list>
<tree><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Kim, Sang Il" sort="Kim, Sang Il" uniqKey="Kim S" first="Sang Il" last="Kim">Sang Il Kim</name>
</region>
<name sortKey="Baek, Songyi" sort="Baek, Songyi" uniqKey="Baek S" first="Songyi" last="Baek">Songyi Baek</name>
<name sortKey="Chang, So Young" sort="Chang, So Young" uniqKey="Chang S" first="So Young" last="Chang">So Young Chang</name>
<name sortKey="Chung, Junho" sort="Chung, Junho" uniqKey="Chung J" first="Junho" last="Chung">Junho Chung</name>
<name sortKey="Jin, Jongwha" sort="Jin, Jongwha" uniqKey="Jin J" first="Jongwha" last="Jin">Jongwha Jin</name>
<name sortKey="Kim, Jinhee" sort="Kim, Jinhee" uniqKey="Kim J" first="Jinhee" last="Kim">Jinhee Kim</name>
<name sortKey="Kim, Seungtaek" sort="Kim, Seungtaek" uniqKey="Kim S" first="Seungtaek" last="Kim">Seungtaek Kim</name>
<name sortKey="Kim, Sujeong" sort="Kim, Sujeong" uniqKey="Kim S" first="Sujeong" last="Kim">Sujeong Kim</name>
<name sortKey="Lim, Chungsu" sort="Lim, Chungsu" uniqKey="Lim C" first="Chungsu" last="Lim">Chungsu Lim</name>
<name sortKey="Min, Ji Young" sort="Min, Ji Young" uniqKey="Min J" first="Ji-Young" last="Min">Ji-Young Min</name>
<name sortKey="Oh, Myoung Don" sort="Oh, Myoung Don" uniqKey="Oh M" first="Myoung-Don" last="Oh">Myoung-Don Oh</name>
<name sortKey="Park, Wan Beom" sort="Park, Wan Beom" uniqKey="Park W" first="Wan Beom" last="Park">Wan Beom Park</name>
<name sortKey="Shim, Jung Min" sort="Shim, Jung Min" uniqKey="Shim J" first="Jung Min" last="Shim">Jung Min Shim</name>
</country>
</tree>
</affiliations>
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   |texte=   Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody.
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Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody.

Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody.

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