A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.
Identifieur interne : 001375 ( Main/Exploration ); précédent : 001374; suivant : 001376A 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 :
- Science translational medicine [ 1946-6242 ] ; 2015.
Descripteurs français
- KwdFr :
- MESH :
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient.
- usage thérapeutique : Vaccins à ADN.
- Animaux, Chameaux, Macaca mulatta, Souris.
English descriptors
- KwdEn :
- MESH :
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- chemical , therapeutic use : Vaccines, DNA.
- Animals, Camelus, Macaca mulatta, Mice.
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
Affiliations:
- Canada, États-Unis
- Floride, Montana, Pennsylvanie, Washington (État)
- Seattle
- Université de Washington
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Le document en format XML
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Ugen</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Sardesai, Niranjan Y" sort="Sardesai, Niranjan Y" uniqKey="Sardesai N" first="Niranjan Y" last="Sardesai">Niranjan Y. Sardesai</name><affiliation wicri:level="2"><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Kim, J Joseph" sort="Kim, J Joseph" uniqKey="Kim J" first="J Joseph" last="Kim">J Joseph Kim</name><affiliation wicri:level="2"><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Kobinger, Gary" sort="Kobinger, Gary" uniqKey="Kobinger G" first="Gary" last="Kobinger">Gary Kobinger</name><affiliation wicri:level="1"><nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2</wicri:regionArea><wicri:noRegion>Manitoba R3E 3R2</wicri:noRegion></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Weiner, David B" sort="Weiner, David B" uniqKey="Weiner D" first="David B" last="Weiner">David B. Weiner</name><affiliation wicri:level="2"><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><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26290414</idno><idno type="pmid">26290414</idno><idno type="doi">10.1126/scitranslmed.aac7462</idno><idno type="wicri:Area/PubMed/Corpus">000D82</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000D82</idno><idno type="wicri:Area/PubMed/Curation">000D82</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000D82</idno><idno type="wicri:Area/PubMed/Checkpoint">000E67</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000E67</idno><idno type="wicri:Area/Ncbi/Merge">002B13</idno><idno type="wicri:Area/Ncbi/Curation">002B13</idno><idno type="wicri:Area/Ncbi/Checkpoint">002B13</idno><idno type="wicri:Area/Main/Merge">001377</idno><idno type="wicri:Area/Main/Curation">001375</idno><idno type="wicri:Area/Main/Exploration">001375</idno></publicationStmt><sourceDesc><biblStruct><analytic><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><author><name sortKey="Muthumani, Karuppiah" sort="Muthumani, Karuppiah" uniqKey="Muthumani K" first="Karuppiah" last="Muthumani">Karuppiah Muthumani</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Falzarano, Darryl" sort="Falzarano, Darryl" uniqKey="Falzarano D" first="Darryl" last="Falzarano">Darryl Falzarano</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Reuschel, Emma L" sort="Reuschel, Emma L" uniqKey="Reuschel E" first="Emma L" last="Reuschel">Emma L. Reuschel</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Tingey, Colleen" sort="Tingey, Colleen" uniqKey="Tingey C" first="Colleen" last="Tingey">Colleen Tingey</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Flingai, Seleeke" sort="Flingai, Seleeke" uniqKey="Flingai S" first="Seleeke" last="Flingai">Seleeke Flingai</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Villarreal, Daniel O" sort="Villarreal, Daniel O" uniqKey="Villarreal D" first="Daniel O" last="Villarreal">Daniel O. Villarreal</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Wise, Megan" sort="Wise, Megan" uniqKey="Wise M" first="Megan" last="Wise">Megan Wise</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Patel, Ami" sort="Patel, Ami" uniqKey="Patel A" first="Ami" last="Patel">Ami Patel</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Izmirly, Abdullah" sort="Izmirly, Abdullah" uniqKey="Izmirly A" first="Abdullah" last="Izmirly">Abdullah Izmirly</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Aljuaid, Abdulelah" sort="Aljuaid, Abdulelah" uniqKey="Aljuaid A" first="Abdulelah" last="Aljuaid">Abdulelah Aljuaid</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Seliga, Alecia M" sort="Seliga, Alecia M" uniqKey="Seliga A" first="Alecia M" last="Seliga">Alecia M. Seliga</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Soule, Geoff" sort="Soule, Geoff" uniqKey="Soule G" first="Geoff" last="Soule">Geoff Soule</name><affiliation wicri:level="1"><nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2</wicri:regionArea><wicri:noRegion>Manitoba R3E 3R2</wicri:noRegion></affiliation></author><author><name sortKey="Morrow, Matthew" sort="Morrow, Matthew" uniqKey="Morrow M" first="Matthew" last="Morrow">Matthew Morrow</name><affiliation wicri:level="2"><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Kraynyak, Kimberly A" sort="Kraynyak, Kimberly A" uniqKey="Kraynyak K" first="Kimberly A" last="Kraynyak">Kimberly A. Kraynyak</name><affiliation wicri:level="2"><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Khan, Amir S" sort="Khan, Amir S" uniqKey="Khan A" first="Amir S" last="Khan">Amir S. Khan</name><affiliation wicri:level="2"><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Scott, Dana P" sort="Scott, Dana P" uniqKey="Scott D" first="Dana P" last="Scott">Dana P. Scott</name><affiliation wicri:level="2"><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><affiliation wicri:level="2"><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Lacasse, Rachel" sort="Lacasse, Rachel" uniqKey="Lacasse R" first="Rachel" last="Lacasse">Rachel Lacasse</name><affiliation wicri:level="2"><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Meade White, Kimberly" sort="Meade White, Kimberly" uniqKey="Meade White K" first="Kimberly" last="Meade-White">Kimberly Meade-White</name><affiliation wicri:level="2"><nlm:affiliation>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology, University of Washington, Seattle, WA 98195, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Washington, Seattle, WA 98195</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Ugen, Kenneth E" sort="Ugen, Kenneth E" uniqKey="Ugen K" first="Kenneth E" last="Ugen">Kenneth E. Ugen</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Sardesai, Niranjan Y" sort="Sardesai, Niranjan Y" uniqKey="Sardesai N" first="Niranjan Y" last="Sardesai">Niranjan Y. Sardesai</name><affiliation wicri:level="2"><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Kim, J Joseph" sort="Kim, J Joseph" uniqKey="Kim J" first="J Joseph" last="Kim">J Joseph Kim</name><affiliation wicri:level="2"><nlm:affiliation>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Kobinger, Gary" sort="Kobinger, Gary" uniqKey="Kobinger G" first="Gary" last="Kobinger">Gary Kobinger</name><affiliation wicri:level="1"><nlm:affiliation>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, University of Manitoba and Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2</wicri:regionArea><wicri:noRegion>Manitoba R3E 3R2</wicri:noRegion></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840</wicri:regionArea><placeName><region type="state">Montana</region></placeName></affiliation></author><author><name sortKey="Weiner, David B" sort="Weiner, David B" uniqKey="Weiner D" first="David B" last="Weiner">David B. Weiner</name><affiliation wicri:level="2"><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><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><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><keywords scheme="KwdFr" xml:lang="fr"><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><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><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><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Vaccines, DNA</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Vaccins à ADN</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Camelus</term><term>Macaca mulatta</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Chameaux</term><term>Macaca mulatta</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><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></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Floride</li><li>Montana</li><li>Pennsylvanie</li><li>Washington (État)</li></region><settlement><li>Seattle</li></settlement><orgName><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Muthumani, Karuppiah" sort="Muthumani, Karuppiah" uniqKey="Muthumani K" first="Karuppiah" last="Muthumani">Karuppiah Muthumani</name></region><name sortKey="Aljuaid, Abdulelah" sort="Aljuaid, Abdulelah" uniqKey="Aljuaid A" first="Abdulelah" last="Aljuaid">Abdulelah Aljuaid</name><name sortKey="Falzarano, Darryl" sort="Falzarano, Darryl" uniqKey="Falzarano D" first="Darryl" last="Falzarano">Darryl Falzarano</name><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><name sortKey="Flingai, Seleeke" sort="Flingai, Seleeke" uniqKey="Flingai S" first="Seleeke" last="Flingai">Seleeke Flingai</name><name sortKey="Izmirly, Abdullah" sort="Izmirly, Abdullah" uniqKey="Izmirly A" first="Abdullah" last="Izmirly">Abdullah Izmirly</name><name sortKey="Khan, Amir S" sort="Khan, Amir S" uniqKey="Khan A" first="Amir S" last="Khan">Amir S. Khan</name><name sortKey="Kim, J Joseph" sort="Kim, J Joseph" uniqKey="Kim J" first="J Joseph" last="Kim">J Joseph Kim</name><name sortKey="Kraynyak, Kimberly A" sort="Kraynyak, Kimberly A" uniqKey="Kraynyak K" first="Kimberly A" last="Kraynyak">Kimberly A. Kraynyak</name><name sortKey="Lacasse, Rachel" sort="Lacasse, Rachel" uniqKey="Lacasse R" first="Rachel" last="Lacasse">Rachel Lacasse</name><name sortKey="Meade White, Kimberly" sort="Meade White, Kimberly" uniqKey="Meade White K" first="Kimberly" last="Meade-White">Kimberly Meade-White</name><name sortKey="Morrow, Matthew" sort="Morrow, Matthew" uniqKey="Morrow M" first="Matthew" last="Morrow">Matthew Morrow</name><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><name sortKey="Patel, Ami" sort="Patel, Ami" uniqKey="Patel A" first="Ami" last="Patel">Ami Patel</name><name sortKey="Reuschel, Emma L" sort="Reuschel, Emma L" uniqKey="Reuschel E" first="Emma L" last="Reuschel">Emma L. Reuschel</name><name sortKey="Sardesai, Niranjan Y" sort="Sardesai, Niranjan Y" uniqKey="Sardesai N" first="Niranjan Y" last="Sardesai">Niranjan Y. Sardesai</name><name sortKey="Scott, Dana P" sort="Scott, Dana P" uniqKey="Scott D" first="Dana P" last="Scott">Dana P. Scott</name><name sortKey="Seliga, Alecia M" sort="Seliga, Alecia M" uniqKey="Seliga A" first="Alecia M" last="Seliga">Alecia M. Seliga</name><name sortKey="Tingey, Colleen" sort="Tingey, Colleen" uniqKey="Tingey C" first="Colleen" last="Tingey">Colleen Tingey</name><name sortKey="Ugen, Kenneth E" sort="Ugen, Kenneth E" uniqKey="Ugen K" first="Kenneth E" last="Ugen">Kenneth E. Ugen</name><name sortKey="Villarreal, Daniel O" sort="Villarreal, Daniel O" uniqKey="Villarreal D" first="Daniel O" last="Villarreal">Daniel O. Villarreal</name><name sortKey="Weiner, David B" sort="Weiner, David B" uniqKey="Weiner D" first="David B" last="Weiner">David B. Weiner</name><name sortKey="Wise, Megan" sort="Wise, Megan" uniqKey="Wise M" first="Megan" last="Wise">Megan Wise</name></country><country name="Canada"><noRegion><name sortKey="Soule, Geoff" sort="Soule, Geoff" uniqKey="Soule G" first="Geoff" last="Soule">Geoff Soule</name></noRegion><name sortKey="Kobinger, Gary" sort="Kobinger, Gary" uniqKey="Kobinger G" first="Gary" last="Kobinger">Gary Kobinger</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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