Serveur d'exploration MERS

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A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.

Identifieur interne : 001236 ( Ncbi/Merge ); précédent : 001235; suivant : 001237

A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.

Auteurs : Karuppiah Muthumani [États-Unis] ; Darryl Falzarano [États-Unis] ; Emma L. Reuschel [États-Unis] ; Colleen Tingey [États-Unis] ; Seleeke Flingai [États-Unis] ; Daniel O. Villarreal [États-Unis] ; Megan Wise [États-Unis] ; Ami Patel [États-Unis] ; Abdullah Izmirly [États-Unis] ; Abdulelah Aljuaid [États-Unis] ; Alecia M. Seliga [États-Unis] ; Geoff Soule [Canada] ; Matthew Morrow [États-Unis] ; Kimberly A. Kraynyak [États-Unis] ; Amir S. Khan [États-Unis] ; Dana P. Scott [États-Unis] ; Friederike Feldmann [États-Unis] ; Rachel Lacasse [États-Unis] ; Kimberly Meade-White [États-Unis] ; Atsushi Okumura [États-Unis] ; Kenneth E. Ugen [États-Unis] ; Niranjan Y. Sardesai [États-Unis] ; J Joseph Kim [États-Unis] ; Gary Kobinger [Canada] ; Heinz Feldmann [États-Unis] ; David B. Weiner [États-Unis]

Source :

RBID : pubmed:26290414

Descripteurs français

English descriptors

Abstract

First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.

DOI: 10.1126/scitranslmed.aac7462
PubMed: 26290414

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pubmed:26290414

Le document en format XML

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<name sortKey="Patel, Ami" sort="Patel, Ami" uniqKey="Patel A" first="Ami" last="Patel">Ami Patel</name>
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<name sortKey="Aljuaid, Abdulelah" sort="Aljuaid, Abdulelah" uniqKey="Aljuaid A" first="Abdulelah" last="Aljuaid">Abdulelah Aljuaid</name>
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<name sortKey="Seliga, Alecia M" sort="Seliga, Alecia M" uniqKey="Seliga A" first="Alecia M" last="Seliga">Alecia M. Seliga</name>
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<name sortKey="Kraynyak, Kimberly A" sort="Kraynyak, Kimberly A" uniqKey="Kraynyak K" first="Kimberly A" last="Kraynyak">Kimberly A. Kraynyak</name>
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<name sortKey="Khan, Amir S" sort="Khan, Amir S" uniqKey="Khan A" first="Amir S" last="Khan">Amir S. Khan</name>
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<name sortKey="Scott, Dana P" sort="Scott, Dana P" uniqKey="Scott D" first="Dana P" last="Scott">Dana P. Scott</name>
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<name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name>
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<name sortKey="Lacasse, Rachel" sort="Lacasse, Rachel" uniqKey="Lacasse R" first="Rachel" last="Lacasse">Rachel Lacasse</name>
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<name sortKey="Meade White, Kimberly" sort="Meade White, Kimberly" uniqKey="Meade White K" first="Kimberly" last="Meade-White">Kimberly Meade-White</name>
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<name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name>
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<nlm:affiliation>Department of Microbiology, University of Washington, Seattle, WA 98195, USA.</nlm:affiliation>
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<name sortKey="Ugen, Kenneth E" sort="Ugen, Kenneth E" uniqKey="Ugen K" first="Kenneth E" last="Ugen">Kenneth E. Ugen</name>
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<nlm:affiliation>Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.</nlm:affiliation>
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<name sortKey="Sardesai, Niranjan Y" sort="Sardesai, Niranjan Y" uniqKey="Sardesai N" first="Niranjan Y" last="Sardesai">Niranjan Y. Sardesai</name>
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<nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
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<name sortKey="Kim, J Joseph" sort="Kim, J Joseph" uniqKey="Kim J" first="J Joseph" last="Kim">J Joseph Kim</name>
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<name sortKey="Kobinger, Gary" sort="Kobinger, Gary" uniqKey="Kobinger G" first="Gary" last="Kobinger">Gary Kobinger</name>
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<nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation>
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<name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name>
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<country xml:lang="fr">États-Unis</country>
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<wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea>
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<title xml:lang="en">A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.</title>
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<name sortKey="Reuschel, Emma L" sort="Reuschel, Emma L" uniqKey="Reuschel E" first="Emma L" last="Reuschel">Emma L. Reuschel</name>
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<nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
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<name sortKey="Flingai, Seleeke" sort="Flingai, Seleeke" uniqKey="Flingai S" first="Seleeke" last="Flingai">Seleeke Flingai</name>
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<name sortKey="Villarreal, Daniel O" sort="Villarreal, Daniel O" uniqKey="Villarreal D" first="Daniel O" last="Villarreal">Daniel O. Villarreal</name>
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<name sortKey="Wise, Megan" sort="Wise, Megan" uniqKey="Wise M" first="Megan" last="Wise">Megan Wise</name>
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<nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation>
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<region type="state">Montana</region>
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<region type="state">Montana</region>
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<name sortKey="Lacasse, Rachel" sort="Lacasse, Rachel" uniqKey="Lacasse R" first="Rachel" last="Lacasse">Rachel Lacasse</name>
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<country xml:lang="fr">États-Unis</country>
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<country xml:lang="fr">États-Unis</country>
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<name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name>
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<region type="state">Floride</region>
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<name sortKey="Sardesai, Niranjan Y" sort="Sardesai, Niranjan Y" uniqKey="Sardesai N" first="Niranjan Y" last="Sardesai">Niranjan Y. Sardesai</name>
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<name sortKey="Kim, J Joseph" sort="Kim, J Joseph" uniqKey="Kim J" first="J Joseph" last="Kim">J Joseph Kim</name>
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<nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation>
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<region type="state">Pennsylvanie</region>
</placeName>
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<name sortKey="Kobinger, Gary" sort="Kobinger, Gary" uniqKey="Kobinger G" first="Gary" last="Kobinger">Gary Kobinger</name>
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<nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation>
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<name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name>
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<region type="state">Montana</region>
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<name sortKey="Weiner, David B" sort="Weiner, David B" uniqKey="Weiner D" first="David B" last="Weiner">David B. Weiner</name>
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<nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA. dbweiner@mail.med.upenn.edu.</nlm:affiliation>
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<title level="j">Science translational medicine</title>
<idno type="eISSN">1946-6242</idno>
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<term>Animals</term>
<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Camelus</term>
<term>Macaca mulatta</term>
<term>Mice</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Vaccines, DNA (therapeutic use)</term>
</keywords>
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<term>Animaux</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Chameaux</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Macaca mulatta</term>
<term>Souris</term>
<term>Vaccins à ADN (usage thérapeutique)</term>
</keywords>
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<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
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<term>Vaccines, DNA</term>
</keywords>
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<term>Vaccins à ADN</term>
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<div type="abstract" xml:lang="en">First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.</div>
</front>
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<DateCompleted>
<Year>2016</Year>
<Month>05</Month>
<Day>17</Day>
</DateCompleted>
<DateRevised>
<Year>2019</Year>
<Month>01</Month>
<Day>08</Day>
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<ISSN IssnType="Electronic">1946-6242</ISSN>
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<Volume>7</Volume>
<Issue>301</Issue>
<PubDate>
<Year>2015</Year>
<Month>Aug</Month>
<Day>19</Day>
</PubDate>
</JournalIssue>
<Title>Science translational medicine</Title>
<ISOAbbreviation>Sci Transl Med</ISOAbbreviation>
</Journal>
<ArticleTitle>A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.</ArticleTitle>
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<MedlinePgn>301ra132</MedlinePgn>
</Pagination>
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<Abstract>
<AbstractText>First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.</AbstractText>
<CopyrightInformation>Copyright © 2015, American Association for the Advancement of Science.</CopyrightInformation>
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<LastName>Okumura</LastName>
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<LastName>Ugen</LastName>
<ForeName>Kenneth E</ForeName>
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<Affiliation>Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.</Affiliation>
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