Airway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses
Identifieur interne : 000739 ( Pmc/Checkpoint ); précédent : 000738; suivant : 000740Airway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses
Auteurs : Jincun Zhao [République populaire de Chine, États-Unis] ; Jingxian Zhao [États-Unis] ; Ashutosh K. Mangalam [États-Unis] ; Rudragouda Channappanavar [États-Unis] ; Craig Fett [États-Unis] ; David K. Meyerholz [États-Unis] ; Sudhakar Agnihothram [États-Unis] ; Ralph S. Baric [États-Unis] ; Chella S. David [États-Unis] ; Stanley Perlman [États-Unis]Source :
- Immunity [ 1074-7613 ] ; 2016.
Abstract
Two zoonotic coronaviruses (CoVs)—SARS-CoV and MERS-CoV—have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4+ T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4+ T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was dependent on interferon-γ and required early induction of robust innate and virus-specific CD8+ T cell responses. The conserved epitope was also recognized in SARS-CoV- and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4+ T cells targeting conserved epitopes might have broad applicability in the context of new CoVs and other respiratory virus outbreaks.
Url:
DOI: 10.1016/j.immuni.2016.05.006
PubMed: 27287409
PubMed Central: 4917442
Affiliations:
- République populaire de Chine, États-Unis
- Caroline du Nord, Guangdong, Iowa, Michigan
- Iowa City, Jiangmen
- Université de l'Iowa
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PMC:4917442Le document en format XML
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T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses</title>
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<author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name>
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<author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
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<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p>Two zoonotic coronaviruses (CoVs)—SARS-CoV and MERS-CoV—have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4<sup>+</sup>
T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4<sup>+</sup>
T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was dependent on interferon-γ and required early induction of robust innate and virus-specific CD8<sup>+</sup>
T cell responses. The conserved epitope was also recognized in SARS-CoV- and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4<sup>+</sup>
T cells targeting conserved epitopes might have broad applicability in the context of new CoVs and other respiratory virus outbreaks.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Immunity</journal-id>
<journal-id journal-id-type="iso-abbrev">Immunity</journal-id>
<journal-title-group><journal-title>Immunity</journal-title>
</journal-title-group>
<issn pub-type="ppub">1074-7613</issn>
<issn pub-type="epub">1097-4180</issn>
<publisher><publisher-name>Elsevier Inc.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">27287409</article-id>
<article-id pub-id-type="pmc">4917442</article-id>
<article-id pub-id-type="publisher-id">S1074-7613(16)30160-1</article-id>
<article-id pub-id-type="doi">10.1016/j.immuni.2016.05.006</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Airway Memory CD4<sup>+</sup>
T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" id="au1"><name><surname>Zhao</surname>
<given-names>Jincun</given-names>
</name>
<email>zhaojincun@gird.cn</email>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="fn1" ref-type="fn">6</xref>
<xref rid="cor1" ref-type="corresp">∗</xref>
</contrib>
<contrib contrib-type="author" id="au2"><name><surname>Zhao</surname>
<given-names>Jingxian</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="fn1" ref-type="fn">6</xref>
</contrib>
<contrib contrib-type="author" id="au3"><name><surname>Mangalam</surname>
<given-names>Ashutosh K.</given-names>
</name>
<xref rid="aff3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author" id="au4"><name><surname>Channappanavar</surname>
<given-names>Rudragouda</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au5"><name><surname>Fett</surname>
<given-names>Craig</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au6"><name><surname>Meyerholz</surname>
<given-names>David K.</given-names>
</name>
<xref rid="aff3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author" id="au7"><name><surname>Agnihothram</surname>
<given-names>Sudhakar</given-names>
</name>
<xref rid="aff4" ref-type="aff">4</xref>
<xref rid="fn2" ref-type="fn">7</xref>
</contrib>
<contrib contrib-type="author" id="au8"><name><surname>Baric</surname>
<given-names>Ralph S.</given-names>
</name>
<xref rid="aff4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author" id="au9"><name><surname>David</surname>
<given-names>Chella S.</given-names>
</name>
<xref rid="aff5" ref-type="aff">5</xref>
</contrib>
<contrib contrib-type="author" id="au10"><name><surname>Perlman</surname>
<given-names>Stanley</given-names>
</name>
<email>stanley-perlman@uiowa.edu</email>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="cor2" ref-type="corresp">∗∗</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China</aff>
<aff id="aff2"><label>2</label>
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA</aff>
<aff id="aff3"><label>3</label>
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA</aff>
<aff id="aff4"><label>4</label>
Department of Microbiology and Immunology and Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA</aff>
<aff id="aff5"><label>5</label>
Department of Immunology, Mayo Clinic, Rochester, MI 55905, USA</aff>
<author-notes><corresp id="cor1"><label>∗</label>
Corresponding author <email>zhaojincun@gird.cn</email>
</corresp>
<corresp id="cor2"><label>∗∗</label>
Corresponding author <email>stanley-perlman@uiowa.edu</email>
</corresp>
<fn id="fn1"><label>6</label>
<p id="ntpara0010">Co-first author</p>
</fn>
<fn id="fn2"><label>7</label>
<p id="ntpara0015">Present address: National Center for Toxicological Research, Food and Drug Administration, Jefferson, AK 72079, USA</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release"><day>7</day>
<month>6</month>
<year>2016</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>21</day>
<month>6</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="epub"><day>7</day>
<month>6</month>
<year>2016</year>
</pub-date>
<volume>44</volume>
<issue>6</issue>
<fpage>1379</fpage>
<lpage>1391</lpage>
<history><date date-type="received"><day>19</day>
<month>11</month>
<year>2015</year>
</date>
<date date-type="rev-recd"><day>14</day>
<month>2</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>8</day>
<month>3</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© 2016 Elsevier Inc.</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>Elsevier Inc.</copyright-holder>
<license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p>
</license>
</permissions>
<abstract id="abs0010"><title>Summary</title>
<p>Two zoonotic coronaviruses (CoVs)—SARS-CoV and MERS-CoV—have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4<sup>+</sup>
T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4<sup>+</sup>
T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was dependent on interferon-γ and required early induction of robust innate and virus-specific CD8<sup>+</sup>
T cell responses. The conserved epitope was also recognized in SARS-CoV- and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4<sup>+</sup>
T cells targeting conserved epitopes might have broad applicability in the context of new CoVs and other respiratory virus outbreaks.</p>
</abstract>
<abstract abstract-type="author-highlights" id="abs0015"><title>Highlights</title>
<p><list list-type="simple" id="ulist0010"><list-item id="u0010"><label>•</label>
<p id="p0010">Intranasal but not subcutaneous vaccination protects mice from pathogenic human CoVs</p>
</list-item>
<list-item id="u0015"><label>•</label>
<p id="p0015">Protection is mediated by airway memory CD4<sup>+</sup>
T cells</p>
</list-item>
<list-item id="u0020"><label>•</label>
<p id="p0020">IFN-γ produced by airway memory CD4<sup>+</sup>
T cells is required for protection</p>
</list-item>
<list-item id="u0025"><label>•</label>
<p id="p0025">A conserved epitope in SARS-CoV and MERS-CoV induces cross-reactive T cell responses</p>
</list-item>
</list>
</p>
</abstract>
<abstract abstract-type="teaser" id="abs0020"><p>Zoonotic CoVs have emerged twice in the past 10 years and have caused severe human respiratory disease. Using an alphavirus vaccine vector, Perlman and colleagues show that intranasal vaccination induces airway memory CD4<sup>+</sup>
T cell responses that protect mice from lethal challenge and are cross-reactive to different CoVs.</p>
</abstract>
</article-meta>
<notes><p id="misc0010">Published: June 7, 2016</p>
</notes>
</front>
</pmc>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
<li>Guangdong</li>
<li>Iowa</li>
<li>Michigan</li>
</region>
<settlement><li>Iowa City</li>
<li>Jiangmen</li>
</settlement>
<orgName><li>Université de l'Iowa</li>
</orgName>
</list>
<tree><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name>
</region>
</country>
<country name="États-Unis"><region name="Iowa"><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name>
</region>
<name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
<name sortKey="Channappanavar, Rudragouda" sort="Channappanavar, Rudragouda" uniqKey="Channappanavar R" first="Rudragouda" last="Channappanavar">Rudragouda Channappanavar</name>
<name sortKey="David, Chella S" sort="David, Chella S" uniqKey="David C" first="Chella S." last="David">Chella S. David</name>
<name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name>
<name sortKey="Mangalam, Ashutosh K" sort="Mangalam, Ashutosh K" uniqKey="Mangalam A" first="Ashutosh K." last="Mangalam">Ashutosh K. Mangalam</name>
<name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name>
<name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<name sortKey="Zhao, Jingxian" sort="Zhao, Jingxian" uniqKey="Zhao J" first="Jingxian" last="Zhao">Jingxian Zhao</name>
</country>
</tree>
</affiliations>
</record>
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