Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model
Identifieur interne : 000346 ( Ncbi/Checkpoint ); précédent : 000345; suivant : 000347Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model
Auteurs : Mark J. Cameron [Canada] ; Alyson A. Kelvin [Canada] ; Alberto J. Leon [Canada, République populaire de Chine] ; Cheryl M. Cameron [Canada] ; Longsi Ran [Canada] ; Luoling Xu [Canada] ; Yong-Kyu Chu [États-Unis] ; Ali Danesh [Canada] ; Yuan Fang [Canada] ; Qianjun Li [États-Unis] ; Austin Anderson [États-Unis] ; Ronald C. Couch [États-Unis] ; Stephane G. Paquette [Canada] ; Ndingsa G. Fomukong [États-Unis] ; Otfried Kistner [Autriche] ; Manfred Lauchart [Autriche] ; Thomas Rowe [Canada] ; Kevin S. Harrod [États-Unis] ; Colleen B. Jonsson [États-Unis] ; David J. Kelvin [Canada, République populaire de Chine, États-Unis, Italie]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)3-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.
Url:
DOI: 10.1371/journal.pone.0045842
PubMed: 23029269
PubMed Central: 3454321
Affiliations:
- Autriche, Canada, Italie, République populaire de Chine, États-Unis
- Alabama, Kentucky, Nouveau-Mexique, Ontario, Vienne (Autriche)
- Toronto, Vienne (Autriche)
- Université de Toronto
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PMC:3454321Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model</title>
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<country xml:lang="fr">Canada</country>
<wicri:regionArea>Immune Diagnostics & Research, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Leon, Alberto J" sort="Leon, Alberto J" uniqKey="Leon A" first="Alberto J." last="Leon">Alberto J. Leon</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong</wicri:regionArea>
<wicri:noRegion>Guangdong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cameron, Cheryl M" sort="Cameron, Cheryl M" uniqKey="Cameron C" first="Cheryl M." last="Cameron">Cheryl M. Cameron</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ran, Longsi" sort="Ran, Longsi" uniqKey="Ran L" first="Longsi" last="Ran">Longsi Ran</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Xu, Luoling" sort="Xu, Luoling" uniqKey="Xu L" first="Luoling" last="Xu">Luoling Xu</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chu, Yong Kyu" sort="Chu, Yong Kyu" uniqKey="Chu Y" first="Yong-Kyu" last="Chu">Yong-Kyu Chu</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, Alabama, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, Alabama</wicri:regionArea>
<placeName><region type="state">Alabama</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Danesh, Ali" sort="Danesh, Ali" uniqKey="Danesh A" first="Ali" last="Danesh">Ali Danesh</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Qianjun" sort="Li, Qianjun" uniqKey="Li Q" first="Qianjun" last="Li">Qianjun Li</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, Alabama, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, Alabama</wicri:regionArea>
<placeName><region type="state">Alabama</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Anderson, Austin" sort="Anderson, Austin" uniqKey="Anderson A" first="Austin" last="Anderson">Austin Anderson</name>
<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, Alabama, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, Alabama</wicri:regionArea>
<placeName><region type="state">Alabama</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Couch, Ronald C" sort="Couch, Ronald C" uniqKey="Couch R" first="Ronald C." last="Couch">Ronald C. Couch</name>
<affiliation wicri:level="2"><nlm:aff id="aff7"><addr-line>Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lovelace Respiratory Research Institute, Albuquerque, New Mexico</wicri:regionArea>
<placeName><region type="state">Nouveau-Mexique</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Paquette, Stephane G" sort="Paquette, Stephane G" uniqKey="Paquette S" first="Stephane G." last="Paquette">Stephane G. Paquette</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fomukong, Ndingsa G" sort="Fomukong, Ndingsa G" uniqKey="Fomukong N" first="Ndingsa G." last="Fomukong">Ndingsa G. Fomukong</name>
<affiliation wicri:level="2"><nlm:aff id="aff7"><addr-line>Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lovelace Respiratory Research Institute, Albuquerque, New Mexico</wicri:regionArea>
<placeName><region type="state">Nouveau-Mexique</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kistner, Otfried" sort="Kistner, Otfried" uniqKey="Kistner O" first="Otfried" last="Kistner">Otfried Kistner</name>
<affiliation wicri:level="3"><nlm:aff id="aff8"><addr-line>Baxter Innovations GmbH, Vienna, Austria</addr-line>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Baxter Innovations GmbH, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lauchart, Manfred" sort="Lauchart, Manfred" uniqKey="Lauchart M" first="Manfred" last="Lauchart">Manfred Lauchart</name>
<affiliation wicri:level="3"><nlm:aff id="aff8"><addr-line>Baxter Innovations GmbH, Vienna, Austria</addr-line>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Baxter Innovations GmbH, Vienna</wicri:regionArea>
<placeName><settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rowe, Thomas" sort="Rowe, Thomas" uniqKey="Rowe T" first="Thomas" last="Rowe">Thomas Rowe</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Harrod, Kevin S" sort="Harrod, Kevin S" uniqKey="Harrod K" first="Kevin S." last="Harrod">Kevin S. Harrod</name>
<affiliation wicri:level="2"><nlm:aff id="aff7"><addr-line>Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lovelace Respiratory Research Institute, Albuquerque, New Mexico</wicri:regionArea>
<placeName><region type="state">Nouveau-Mexique</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jonsson, Colleen B" sort="Jonsson, Colleen B" uniqKey="Jonsson C" first="Colleen B." last="Jonsson">Colleen B. Jonsson</name>
<affiliation wicri:level="2"><nlm:aff id="aff9"><addr-line>Center for Predictive Medicine, Louisville, Kentucky, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Predictive Medicine, Louisville, Kentucky</wicri:regionArea>
<placeName><region type="state">Kentucky</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong</wicri:regionArea>
<wicri:noRegion>Guangdong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff7"><addr-line>Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lovelace Respiratory Research Institute, Albuquerque, New Mexico</wicri:regionArea>
<placeName><region type="state">Nouveau-Mexique</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff11"><addr-line>Sezione di Microbiologia Sperimentale e Clinica, Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Sezione di Microbiologia Sperimentale e Clinica, Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari</wicri:regionArea>
<wicri:noRegion>Sassari</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p>In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)<sub>3</sub>
-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.</p>
</div>
</front>
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<biblStruct><analytic><author><name sortKey="Wentworth, De" uniqKey="Wentworth D">DE Wentworth</name>
</author>
<author><name sortKey="Gillim Ross, L" uniqKey="Gillim Ross L">L Gillim-Ross</name>
</author>
<author><name sortKey="Espina, N" uniqKey="Espina N">N Espina</name>
</author>
<author><name sortKey="Bernard, Ka" uniqKey="Bernard K">KA Bernard</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Banner, D" uniqKey="Banner D">D Banner</name>
</author>
<author><name sortKey="Kelvin, Aa" uniqKey="Kelvin A">AA Kelvin</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Chan, Mc" uniqKey="Chan M">MC Chan</name>
</author>
<author><name sortKey="Chan, Rw" uniqKey="Chan R">RW Chan</name>
</author>
<author><name sortKey="Tsao, Gs" uniqKey="Tsao G">GS Tsao</name>
</author>
<author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Verma, Im" uniqKey="Verma I">IM Verma</name>
</author>
<author><name sortKey="Stevenson, Jk" uniqKey="Stevenson J">JK Stevenson</name>
</author>
<author><name sortKey="Schwarz, Em" uniqKey="Schwarz E">EM Schwarz</name>
</author>
<author><name sortKey="Van, Ad" uniqKey="Van A">AD Van</name>
</author>
<author><name sortKey="Miyamoto, S" uniqKey="Miyamoto S">S Miyamoto</name>
</author>
</analytic>
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</TEI>
<affiliations><list><country><li>Autriche</li>
<li>Canada</li>
<li>Italie</li>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Alabama</li>
<li>Kentucky</li>
<li>Nouveau-Mexique</li>
<li>Ontario</li>
<li>Vienne (Autriche)</li>
</region>
<settlement><li>Toronto</li>
<li>Vienne (Autriche)</li>
</settlement>
<orgName><li>Université de Toronto</li>
</orgName>
</list>
<tree><country name="Canada"><noRegion><name sortKey="Cameron, Mark J" sort="Cameron, Mark J" uniqKey="Cameron M" first="Mark J." last="Cameron">Mark J. Cameron</name>
</noRegion>
<name sortKey="Cameron, Cheryl M" sort="Cameron, Cheryl M" uniqKey="Cameron C" first="Cheryl M." last="Cameron">Cheryl M. Cameron</name>
<name sortKey="Cameron, Cheryl M" sort="Cameron, Cheryl M" uniqKey="Cameron C" first="Cheryl M." last="Cameron">Cheryl M. Cameron</name>
<name sortKey="Cameron, Mark J" sort="Cameron, Mark J" uniqKey="Cameron M" first="Mark J." last="Cameron">Mark J. Cameron</name>
<name sortKey="Danesh, Ali" sort="Danesh, Ali" uniqKey="Danesh A" first="Ali" last="Danesh">Ali Danesh</name>
<name sortKey="Danesh, Ali" sort="Danesh, Ali" uniqKey="Danesh A" first="Ali" last="Danesh">Ali Danesh</name>
<name sortKey="Danesh, Ali" sort="Danesh, Ali" uniqKey="Danesh A" first="Ali" last="Danesh">Ali Danesh</name>
<name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name>
<name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name>
<name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name>
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<name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name>
<name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name>
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<name sortKey="Jonsson, Colleen B" sort="Jonsson, Colleen B" uniqKey="Jonsson C" first="Colleen B." last="Jonsson">Colleen B. Jonsson</name>
<name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name>
<name sortKey="Li, Qianjun" sort="Li, Qianjun" uniqKey="Li Q" first="Qianjun" last="Li">Qianjun Li</name>
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<country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Kistner, Otfried" sort="Kistner, Otfried" uniqKey="Kistner O" first="Otfried" last="Kistner">Otfried Kistner</name>
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<name sortKey="Lauchart, Manfred" sort="Lauchart, Manfred" uniqKey="Lauchart M" first="Manfred" last="Lauchart">Manfred Lauchart</name>
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<country name="Italie"><noRegion><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name>
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