Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses.
Identifieur interne : 000C07 ( PubMed/Curation ); précédent : 000C06; suivant : 000C08Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses.
Auteurs : Jingxian Zhao [République populaire de Chine] ; Abeer N. Alshukairi ; Salim A. Baharoon ; Waleed A. Ahmed ; Ahmad A. Bokhari ; Atef M. Nehdi ; Laila A. Layqah ; Mohammed G. Alghamdi ; Manal M. Al Gethamy ; Ashraf M. Dada ; Imran Khalid ; Mohamad Boujelal ; Sameera M. Al Johani ; Leatrice Vogel [États-Unis] ; Kanta Subbarao [États-Unis] ; Ashutosh Mangalam [États-Unis] ; Chaorong Wu [États-Unis] ; Patrick Ten Eyck [États-Unis] ; Stanley Perlman [États-Unis] ; Jincun Zhao [République populaire de Chine]Source :
- Science immunology [ 2470-9468 ] ; 2017.
Abstract
The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4+ and CD8+ T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT50) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4+ but not CD8+ T cell responses; patients with higher PRNT50 and CD4+ T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8+ T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8+ T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.
DOI: 10.1126/sciimmunol.aan5393
PubMed: 28778905
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Abeer N. Alshukairi<affiliation><nlm:affiliation>King Faisal Specialist Hospital and Research Centre, Jeddah, Kingdom of Saudi Arabia. stanley-perlman@uiowa.edu zhaojincun@gird.cn aalshukairi@kfshrc.edu.sa.</nlm:affiliation>
<wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry>
</affiliation>
<affiliation><nlm:affiliation>King Saud bin Abdulaziz for Health Sciences University, Riyadh, Kingdom of Saudi Arabia.</nlm:affiliation>
<wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry>
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<wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry>
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<affiliation><nlm:affiliation>King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.</nlm:affiliation>
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<affiliation><nlm:affiliation>King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.</nlm:affiliation>
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<affiliation><nlm:affiliation>King Fahd General Hospital, Jeddah, Kingdom of Saudi Arabia.</nlm:affiliation>
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<affiliation><nlm:affiliation>Al Nour Specialist Hospital, Makkah, Kingdom of Saudi Arabia.</nlm:affiliation>
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<author><name sortKey="Zhao, Jingxian" sort="Zhao, Jingxian" uniqKey="Zhao J" first="Jingxian" last="Zhao">Jingxian Zhao</name>
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<author><name sortKey="Baharoon, Salim A" sort="Baharoon, Salim A" uniqKey="Baharoon S" first="Salim A" last="Baharoon">Salim A. Baharoon</name>
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<author><name sortKey="Ahmed, Waleed A" sort="Ahmed, Waleed A" uniqKey="Ahmed W" first="Waleed A" last="Ahmed">Waleed A. Ahmed</name>
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<author><name sortKey="Bokhari, Ahmad A" sort="Bokhari, Ahmad A" uniqKey="Bokhari A" first="Ahmad A" last="Bokhari">Ahmad A. Bokhari</name>
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<author><name sortKey="Nehdi, Atef M" sort="Nehdi, Atef M" uniqKey="Nehdi A" first="Atef M" last="Nehdi">Atef M. Nehdi</name>
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<author><name sortKey="Layqah, Laila A" sort="Layqah, Laila A" uniqKey="Layqah L" first="Laila A" last="Layqah">Laila A. Layqah</name>
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<author><name sortKey="Alghamdi, Mohammed G" sort="Alghamdi, Mohammed G" uniqKey="Alghamdi M" first="Mohammed G" last="Alghamdi">Mohammed G. Alghamdi</name>
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</affiliation>
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<author><name sortKey="Al Gethamy, Manal M" sort="Al Gethamy, Manal M" uniqKey="Al Gethamy M" first="Manal M" last="Al Gethamy">Manal M. Al Gethamy</name>
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</affiliation>
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<author><name sortKey="Dada, Ashraf M" sort="Dada, Ashraf M" uniqKey="Dada A" first="Ashraf M" last="Dada">Ashraf M. Dada</name>
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<wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry>
</affiliation>
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<author><name sortKey="Khalid, Imran" sort="Khalid, Imran" uniqKey="Khalid I" first="Imran" last="Khalid">Imran Khalid</name>
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<wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Boujelal, Mohamad" sort="Boujelal, Mohamad" uniqKey="Boujelal M" first="Mohamad" last="Boujelal">Mohamad Boujelal</name>
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<wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry>
</affiliation>
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<author><name sortKey="Al Johani, Sameera M" sort="Al Johani, Sameera M" uniqKey="Al Johani S" first="Sameera M" last="Al Johani">Sameera M. Al Johani</name>
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<wicri:noCountry code="subField">Kingdom of Saudi Arabia</wicri:noCountry>
</affiliation>
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<author><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea>
</affiliation>
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<author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mangalam, Ashutosh" sort="Mangalam, Ashutosh" uniqKey="Mangalam A" first="Ashutosh" last="Mangalam">Ashutosh Mangalam</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Iowa, Iowa City, IA 52242</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Chaorong" sort="Wu, Chaorong" uniqKey="Wu C" first="Chaorong" last="Wu">Chaorong Wu</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242</wicri:regionArea>
</affiliation>
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<author><name sortKey="Ten Eyck, Patrick" sort="Ten Eyck, Patrick" uniqKey="Ten Eyck P" first="Patrick" last="Ten Eyck">Patrick Ten Eyck</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242</wicri:regionArea>
</affiliation>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182</wicri:regionArea>
</affiliation>
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<front><div type="abstract" xml:lang="en">The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4<sup>+</sup>
and CD8<sup>+</sup>
T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT<sub>50</sub>
) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4<sup>+</sup>
but not CD8<sup>+</sup>
T cell responses; patients with higher PRNT<sub>50</sub>
and CD4<sup>+</sup>
T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8<sup>+</sup>
T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8<sup>+</sup>
T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">28778905</PMID>
<DateRevised><Year>2019</Year>
<Month>11</Month>
<Day>20</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2470-9468</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>2</Volume>
<Issue>14</Issue>
<PubDate><Year>2017</Year>
<Month>Aug</Month>
<Day>04</Day>
</PubDate>
</JournalIssue>
<Title>Science immunology</Title>
<ISOAbbreviation>Sci Immunol</ISOAbbreviation>
</Journal>
<ArticleTitle>Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">eaan5393</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1126/sciimmunol.aan5393</ELocationID>
<Abstract><AbstractText>The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4<sup>+</sup>
and CD8<sup>+</sup>
T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT<sub>50</sub>
) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4<sup>+</sup>
but not CD8<sup>+</sup>
T cell responses; patients with higher PRNT<sub>50</sub>
and CD4<sup>+</sup>
T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8<sup>+</sup>
T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8<sup>+</sup>
T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.</AbstractText>
<CopyrightInformation>Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Jingxian</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-2615-3182</Identifier>
<AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Alshukairi</LastName>
<ForeName>Abeer N</ForeName>
<Initials>AN</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-9565-3527</Identifier>
<AffiliationInfo><Affiliation>King Faisal Specialist Hospital and Research Centre, Jeddah, Kingdom of Saudi Arabia. stanley-perlman@uiowa.edu zhaojincun@gird.cn aalshukairi@kfshrc.edu.sa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Baharoon</LastName>
<ForeName>Salim A</ForeName>
<Initials>SA</Initials>
<AffiliationInfo><Affiliation>King Saud bin Abdulaziz for Health Sciences University, Riyadh, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ahmed</LastName>
<ForeName>Waleed A</ForeName>
<Initials>WA</Initials>
<AffiliationInfo><Affiliation>King Faisal Specialist Hospital and Research Centre, Jeddah, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bokhari</LastName>
<ForeName>Ahmad A</ForeName>
<Initials>AA</Initials>
<AffiliationInfo><Affiliation>King Faisal Specialist Hospital and Research Centre, Jeddah, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nehdi</LastName>
<ForeName>Atef M</ForeName>
<Initials>AM</Initials>
<AffiliationInfo><Affiliation>King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Layqah</LastName>
<ForeName>Laila A</ForeName>
<Initials>LA</Initials>
<AffiliationInfo><Affiliation>King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Alghamdi</LastName>
<ForeName>Mohammed G</ForeName>
<Initials>MG</Initials>
<AffiliationInfo><Affiliation>King Fahd General Hospital, Jeddah, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Al Gethamy</LastName>
<ForeName>Manal M</ForeName>
<Initials>MM</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0001-6574-2214</Identifier>
<AffiliationInfo><Affiliation>Al Nour Specialist Hospital, Makkah, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dada</LastName>
<ForeName>Ashraf M</ForeName>
<Initials>AM</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-9893-7496</Identifier>
<AffiliationInfo><Affiliation>King Faisal Specialist Hospital and Research Centre, Jeddah, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Khalid</LastName>
<ForeName>Imran</ForeName>
<Initials>I</Initials>
<AffiliationInfo><Affiliation>King Faisal Specialist Hospital and Research Centre, Jeddah, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Boujelal</LastName>
<ForeName>Mohamad</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Al Johani</LastName>
<ForeName>Sameera M</ForeName>
<Initials>SM</Initials>
<AffiliationInfo><Affiliation>King Saud bin Abdulaziz for Health Sciences University, Riyadh, Kingdom of Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Vogel</LastName>
<ForeName>Leatrice</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Subbarao</LastName>
<ForeName>Kanta</ForeName>
<Initials>K</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-1713-3056</Identifier>
<AffiliationInfo><Affiliation>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mangalam</LastName>
<ForeName>Ashutosh</ForeName>
<Initials>A</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-9926-2531</Identifier>
<AffiliationInfo><Affiliation>Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wu</LastName>
<ForeName>Chaorong</ForeName>
<Initials>C</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-1569-0978</Identifier>
<AffiliationInfo><Affiliation>Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ten Eyck</LastName>
<ForeName>Patrick</ForeName>
<Initials>P</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-5041-0708</Identifier>
<AffiliationInfo><Affiliation>Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Perlman</LastName>
<ForeName>Stanley</ForeName>
<Initials>S</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-4213-2354</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA. stanley-perlman@uiowa.edu zhaojincun@gird.cn aalshukairi@kfshrc.edu.sa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Jincun</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-2515-5589</Identifier>
<AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China. stanley-perlman@uiowa.edu zhaojincun@gird.cn aalshukairi@kfshrc.edu.sa.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>P01 AI060699</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI091322</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI129269</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U54 TR001356</GrantID>
<Acronym>TR</Acronym>
<Agency>NCATS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>08</Month>
<Day>04</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Sci Immunol</MedlineTA>
<NlmUniqueID>101688624</NlmUniqueID>
<ISSNLinking>2470-9468</ISSNLinking>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year>
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<Day>27</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>06</Month>
<Day>26</Day>
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